本文選題：血管生成 + 含凝血酶敏感素基序I型的解聚素樣金屬蛋白酶　； 參考：《河北北方學(xué)院》2016年碩士論文

【摘要】：原發(fā)性支氣管肺癌(primary bronchogenic carcinoma)的發(fā)病率和死亡率位于各種惡性腫瘤之首,大約85%的肺癌是非小細(xì)胞肺癌,侵襲和轉(zhuǎn)移是肺癌治療失敗的重要原因之一。腫瘤血管生成與惡性腫瘤的侵襲、轉(zhuǎn)移以及治療后復(fù)發(fā)密切相關(guān),血管生成是一個(gè)多基因參與,多步驟循序漸進(jìn)的復(fù)雜過(guò)程,研究血管生成相關(guān)因子及具體的分子機(jī)制為腫瘤的治療提供更多基因位點(diǎn)。因此阻斷血管生成已經(jīng)成為研究腫瘤治療和預(yù)防的熱點(diǎn)。含凝血酶敏感素基序I型的解聚素樣金屬蛋白酶(A disintegrin and metallopeptidase with thrombospondin motif type1,ADAMTS1)是最近發(fā)現(xiàn)的具有抗腫瘤活性的金屬蛋白酶,能夠抑制血管生成,但在肺癌中的功能尚不明確。眾所周知,血管內(nèi)皮生長(zhǎng)因子是在促進(jìn)血管生成方面作用最強(qiáng)的因子,能夠很好的反應(yīng)血管內(nèi)皮的生長(zhǎng)狀態(tài),降低血管內(nèi)皮生長(zhǎng)因子(vascular endothelial growth factor,VEGF)的表達(dá),可以破壞血管生成網(wǎng)絡(luò)進(jìn)而抑制腫瘤生長(zhǎng)。CD105(endoslin,EDG)在惡性腫瘤血管生成、發(fā)生、發(fā)展及生物學(xué)行為中發(fā)揮重要作用。川芎嗪是我國(guó)傳統(tǒng)中醫(yī)藥川芎的有效成分,臨床上普遍用于心腦血管疾病的治療。研究發(fā)現(xiàn)川芎嗪能夠誘導(dǎo)腫瘤細(xì)胞向凋亡方向發(fā)展,提高機(jī)體免疫功抑制血管內(nèi)皮細(xì)胞中促血管生成因子的表達(dá)來(lái)抑制腫瘤的生長(zhǎng)。順鉑為目前臨床上最常用的腫瘤化療藥物之一,能夠作用于多種腫瘤、藥效強(qiáng)、與其他化療藥物聯(lián)用時(shí)能夠增加療效,但長(zhǎng)期使用易產(chǎn)生耐藥。有研究發(fā)現(xiàn),川芎嗪與具有細(xì)胞毒性化療藥物聯(lián)用,可提高抗腫瘤的治療效果。本試驗(yàn)通過(guò)應(yīng)用川芎嗪與順鉑對(duì)接種Lewis肺腺癌細(xì)胞株小鼠進(jìn)行藥物作用后,通過(guò)測(cè)量小鼠腫瘤體積及腫瘤重量的變化,觀察上述藥物對(duì)小鼠移植瘤生長(zhǎng)的影響。同時(shí)通過(guò)應(yīng)用川芎嗪及順鉑對(duì)肺癌移植瘤小鼠進(jìn)行一定的藥物影響,檢測(cè)ADAMTS1、VEGF、MVD-CD105三種蛋白表達(dá)水平的變化,觀察肺癌組織中瘤細(xì)胞及微血管形態(tài)的變化,證實(shí)川芎嗪是否具有抗腫瘤作用,并闡述川芎嗪抗腫瘤血管生成的可能機(jī)制,從而為研究川芎嗪抗腫瘤血管生成可能的發(fā)生機(jī)制以及今后用于臨床治療提供實(shí)驗(yàn)依據(jù)。具體內(nèi)容如下:健康雄性C57BL/6小鼠購(gòu)買(mǎi)后適應(yīng)性喂養(yǎng)一周后,將培養(yǎng)好的Lewis肺腺癌細(xì)胞接種于C57BL/6小鼠右腋下,細(xì)胞液體總量為0.2ml,建立移植瘤模型,2周后接種處皮下可觸及腫塊大小約8mm。按數(shù)字表法將實(shí)驗(yàn)動(dòng)物隨機(jī)分為四組:生理鹽水組,川芎嗪組,順鉑組,聯(lián)合治療組。各組小鼠接種細(xì)胞后在動(dòng)物飼養(yǎng)室內(nèi)常規(guī)飼養(yǎng),接種后2周開(kāi)始按計(jì)劃給藥。生理鹽水組:腹腔注射0.9%氯化鈉0.2 m L,每天1次,連續(xù)14天;順鉑組,腹腔注射2 mgkg-1,順鉑組0.2 m L。每天1次,連續(xù)14天;川芎嗪組,腹腔注射,川芎嗪0.2 m L。每天1次,連續(xù)14天。聯(lián)合組,腹腔注射川芎嗪100 mgkg-1+順鉑2 mgkg-1,共0.2 m L。每天1次,連續(xù)14天。每次給藥前,稱量體重后調(diào)整用藥劑量。實(shí)驗(yàn)小鼠在治療結(jié)束后第5天脫頸法處死,解剖瘤組織,固定液固定。所有瘤組織用電子天平測(cè)量瘤重量,并用游標(biāo)卡尺測(cè)量瘤組織長(zhǎng)短徑,計(jì)算瘤體積,抑瘤率及腫瘤壞死率,透射電鏡觀察瘤組織超微結(jié)構(gòu),免疫組織化學(xué)及蛋白印跡方法檢測(cè)藥物作用前后ADAMTS1、VEGF、微血管密度的變化,微血管密度的變化由CD105染色來(lái)確定。1.治療后小鼠生存質(zhì)量和毒副反應(yīng)的評(píng)估治療方案結(jié)束時(shí),以對(duì)照組小鼠的一般情況為標(biāo)準(zhǔn),通過(guò)精神狀態(tài)、活動(dòng)狀況、飲食情況、體重及腫瘤體積變化等指標(biāo)的觀察,評(píng)估小鼠生存質(zhì)量和對(duì)化療藥物的毒副反應(yīng)。與生理鹽水組比較,川芎嗪組小鼠飲食及活動(dòng)良好,小鼠體重和腫瘤體積增長(zhǎng)幅度相當(dāng)。順鉑組小鼠精神萎靡,飲食量少,活動(dòng)量明顯減少,皮毛缺乏光澤,并出現(xiàn)脫毛現(xiàn)象,喜蜷縮成堆,體重下降最明顯,腫瘤體積比川芎嗪組增長(zhǎng)慢。聯(lián)合治療組小鼠的飲食及活動(dòng)量,皮毛色澤及脫毛程度較順鉑組為好,而差于川芎嗪組。結(jié)果提示:川芎嗪組小鼠用藥后,生存質(zhì)量較好,未產(chǎn)生嚴(yán)重藥物毒副反應(yīng);聯(lián)合治療組小鼠的毒副反應(yīng)輕于順鉑治療組,順鉑組毒副反應(yīng)表現(xiàn)最重,腫瘤體積動(dòng)態(tài)變化情況依次為:生理鹽水組、川芎嗪組、順鉑組、聯(lián)合組,結(jié)果提示川芎嗪與順鉑聯(lián)用能夠降低單用順鉑治療的毒副作用。2.移植瘤小鼠抑瘤率及腫瘤壞死率的觀察藥物治療后觀察移植瘤小鼠腫瘤的抑瘤率:川芎嗪組(35.58%)、順鉑組(40.41%)、聯(lián)合治療組(62.48%),與生理鹽水組比較,各用藥組腫瘤抑瘤率明顯增高,差異有顯著性(P0.05)。移植瘤小鼠腫瘤的壞死率:川芎嗪組(15.58±3.19)、順鉑組(24.64±11.96)以及聯(lián)合治療組(31.76±15.20)腫瘤的壞死高于生理鹽水組(9.37±1.36),差異有顯著性(P0.05)。與順鉑組相比,聯(lián)合治療組移植瘤小鼠抑瘤率、腫瘤壞死率明顯增高,差異有顯著性(P0.05),而順鉑組優(yōu)于川芎嗪組,提示川芎嗪及順鉑聯(lián)合應(yīng)用其抗腫瘤作用優(yōu)于順鉑。3.含凝血酶敏感素基序I型的解聚素樣金屬蛋白酶,血管內(nèi)皮生長(zhǎng)因子,微血管密度在Lewis肺癌組織中的表達(dá)待腫瘤組織全部取出后,免疫組織化學(xué)方法檢測(cè)VEGF、ADAMTS1結(jié)果顯示:VEGF在四組中呈陽(yáng)性表達(dá),與生理鹽水組(56367.82±7441.12)比較,川芎嗪組(28674.58±2331.40)、順鉑組(23932.76±3151.59)以及聯(lián)合治療組(19183.99±1453.64)表達(dá)明顯減少,聯(lián)合治療組表達(dá)最低,差異顯著(P0.05)。ADAMTS1在四組中呈陽(yáng)性表達(dá),川芎嗪組(15475.27±2064.88)、順鉑組(18382.79±2162.08)以及聯(lián)合治療組(26403.85±3293.36)表達(dá)明顯高于對(duì)照組(1646.74±212.96),聯(lián)合治療組表達(dá)最高,生理鹽水組表達(dá)最低,差異顯著(P0.05)。蛋白印跡方法結(jié)果顯示:川芎嗪組(0.57±0.02)、順鉑組(0.79±0.01)、聯(lián)合治療組(0.98±0.02)ADAMTS1的表達(dá)明顯高于生理鹽水組(0.48±0.01),差異顯著(P0.05),而VEGF的表達(dá)生理鹽水組(0.87±0.03)表達(dá)最高,聯(lián)合治療組(0.28±0.01)表達(dá)最低。提示免疫組織化學(xué)方法與蛋白印跡方法結(jié)果基本一致,川芎嗪、順鉑均可降低肺腺癌VEGF的表達(dá),升高其ADAMTS1的表達(dá),川芎嗪聯(lián)合順鉑治療能夠進(jìn)一步增強(qiáng)其抑制VEGF表達(dá)能力,以及促進(jìn)ADAMTS1的表達(dá)能力。4.微血管密度計(jì)數(shù)的檢測(cè)免疫組織化學(xué)方法測(cè)定微血管密度指標(biāo)CD105,光學(xué)顯微鏡下觀察腫瘤血管,參照Weidner法進(jìn)行微血管密度(microvessel density,MVD)的計(jì)數(shù),請(qǐng)病理科專家3名,獨(dú)立觀察5個(gè)高倍視野,最終計(jì)算平均值,結(jié)果表明:生理鹽水組表達(dá)最高(4.9×104±7.3×103),聯(lián)合治療組表達(dá)最低(1.4×104±6.2×103)。5.透射電鏡下觀察腫瘤細(xì)胞形態(tài)及血管結(jié)構(gòu)透射電鏡下結(jié)果顯示生理鹽水組腫瘤細(xì)胞分布密集,細(xì)胞核仁大而明顯,核型不規(guī)則,線粒體及粗面內(nèi)質(zhì)網(wǎng)等細(xì)胞器豐富,偶見(jiàn)凋亡細(xì)胞。川芎嗪組可見(jiàn)部分腫瘤細(xì)胞脂肪變性,胞漿內(nèi)脂滴增多,形成不完整細(xì)胞膜,線粒體空泡化,可見(jiàn)壞死細(xì)胞及碎片,細(xì)胞器減少。順鉑組及聯(lián)合組瘤細(xì)胞分布稀少,可見(jiàn)部分細(xì)胞胞漿線粒體腫脹,可見(jiàn)較多細(xì)胞碎片,常見(jiàn)凋亡腫瘤細(xì)胞,偶見(jiàn)凋亡小體形成。綜上所述,Lewis肺腺癌細(xì)胞接種于C57BL/6小鼠后8~10天,可造模成功。通過(guò)實(shí)驗(yàn)荷瘤小鼠的一般生存狀態(tài)、體重、瘤體積、瘤重、血管超微結(jié)構(gòu)、腫瘤細(xì)胞、血管生成因子的變化,抑瘤率的比較通過(guò)實(shí)驗(yàn)觀察移植瘤小鼠生存狀態(tài)、體重、腫瘤體積、微血管超微結(jié)構(gòu)、血管生成蛋白表達(dá)水平變化,以及腫瘤壞死率及抑瘤率的比較,說(shuō)明川芎嗪與化療藥物順鉑同時(shí)應(yīng)用可提高小鼠生存質(zhì)量,降低毒副反應(yīng);川芎嗪能夠抑制Lewis肺癌小鼠移植瘤生長(zhǎng),與順鉑聯(lián)合具有協(xié)同作用。川芎嗪聯(lián)合順鉑能通過(guò)抑制VEGF表達(dá),促進(jìn)ADAMTS1的表達(dá),減少微血管生成,進(jìn)而抑制腫瘤生長(zhǎng)。
[Abstract]:The incidence and mortality of primary bronchogenic carcinoma (primary bronchogenic carcinoma) are the first of all kinds of malignant tumors. About 85% of the lung cancer is non small cell lung cancer. Invasion and metastasis are one of the important reasons for the failure of lung cancer treatment. Generation is a complex process of multi gene participation and step by step process. The study of angiogenesis related factors and specific molecular mechanisms provides more gene loci for the treatment of tumor. Therefore, blocking angiogenesis has become a hot spot in the study of tumor treatment and prevention. The depolymerization hormone like protease containing thrombin sensitive preorder I (A disintegrin and metallopeptidase with thrombospondin motif Type1, ADAMTS1) is a recently discovered metalloproteinase with antitumor activity, which inhibits angiogenesis, but the function in lung cancer is not clear. It is well known that vascular endothelial growth factor is the strongest factor in promoting angiogenesis and can be very good. The expression of vascular endothelial growth factor (vascular endothelial growth factor, VEGF) can destroy the angiogenesis network and inhibit the growth of.CD105 (endoslin, EDG) and play an important role in the angiogenesis, development, development and biological behavior of malignant tumor. Ligustrazine is a traditional Chinese tradition. The effective components of Ligusticum chuanxiong, a traditional Chinese medicine, are widely used in the treatment of cardiovascular and cerebrovascular diseases. It is found that Ligustrazine can induce tumor cells to develop to the direction of apoptosis and improve the immune function to inhibit the expression of angiogenic factors in vascular endothelial cells to inhibit the growth of tumor. One of the drugs, which can act on a variety of tumors, is potent and can increase the efficacy when combined with other chemotherapeutic drugs, but it is easy to produce drug resistance in the long term. It is found that Ligustrazine is combined with cytotoxic chemotherapeutic drugs to improve the effect of antitumor treatment. This experiment has been conducted with Ligustrazine and cisplatin on Lewis lung adenocarcinoma cells. The effect of the above drugs on the growth of transplanted tumor in mice was observed by measuring the changes of tumor volume and weight of tumor in mice, and the effects of Ligustrazine and cisplatin on the lung cancer transplanted mice were affected by the use of Ligustrazine and cisplatin. The changes of the expression level of the three proteins of ADAMTS1, VEGF and MVD-CD105 were detected and the lung was observed. The changes of tumor cells and microvascular morphology in cancer tissues confirm whether tetramethylpyrazine has anti-tumor effect, and expounds the possible mechanism of Ligustrazine antitumor angiogenesis, thus providing experimental basis for the study of the possible mechanism of Ligustrazine antitumor angiogenesis and clinical treatment in the future. The specific contents are as follows: healthy male C57BL/ After 6 mice were fed for one week after adaptive feeding, the cultured Lewis lung adenocarcinoma cells were inoculated into the right axillary C57BL/6 mice. The total amount of cell liquid was 0.2ml, and the transplanted tumor model was established. After 2 weeks, the size of the palpable mass in the subcutaneous area of the inoculation was divided into four groups randomly: saline group, ligustrazine group and cisplatin group. The mice were inoculated in the treatment group. After inoculation, the mice were fed in the animal feeding room routinely. 2 weeks after inoculation, the saline group was given 0.9% sodium chloride 0.2 m L, 1 times a day for 14 days; cisplatin group, intraperitoneal injection of 2 mg? Kg-1, 0.2 m L. per day for 14 days; Ligustrazine group, intraperitoneal injection of Ligustrazine 0.2 m L. each. 1 times a day for 14 days. The combined group was intraperitoneally injected with Ligustrazine 100 mg? Kg-1+ cisplatin 2 mg? Kg-1, a total of 0.2 m L., 1 times a day for 14 days. The dose of the drug was adjusted after each administration, after weighing the body weight. The experimental mice were sacrificed at fifth days after the treatment, and the tumor tissue and fixed solution were fixed. All tumor tissues measured the weight of the tumor by electronic balance. The length and diameter of tumor tissue were measured with vernier caliper, the tumor volume, tumor suppressor rate and tumor necrosis rate were calculated. The ultrastructure of the tumor tissue was observed by transmission electron microscope. The changes of ADAMTS1, VEGF, microvessel density before and after the action of the drug were detected by immunohistochemistry and Western blot. The changes of microvascular density were determined by CD105 staining to determine the survival quality of the mice after.1. treatment. At the end of the evaluation of the dose and side effects, the general condition of the mice in the control group was taken as the standard. The quality of life and the side effects on the chemotherapeutic drugs were evaluated through the observation of mental state, activity condition, diet, weight and tumor volume, and the diet and activity of the Ligustrazine group in the group of Ligustrazine, compared with the saline group. The body weight and tumor volume increased fairly well. The cisplatin group was depressed, the diet was less, the amount of activity was reduced, the hair lacked luster, and the hair was dehairing, and the body weight decreased most obviously. The volume of tumor was slower than that of the Ligustrazine group. The diet and activity of the mice in the combined treatment group, the color of fur and the hair removal process in the combined treatment group were more than that of the Ligustrazine group. Compared with the cisplatin group, it was better than the Ligustrazine group. The results suggested that the qustrazine group had better quality of survival and no serious drug side effects after the use of the tetramethylpyrazine group. The side effects of the combined treatment group were less than the cisplatin treatment group. The side effects of the cisplatin group were the heaviest, and the dynamic changes of the tumor volume were in the normal saline group, the Ligustrazine group, and the group of tetramethylpyrazine. The combination of cisplatin and cisplatin, the results suggest that the combination of Ligustrazine and cisplatin can reduce the tumor suppressor rate and tumor necrosis rate of.2. transplanted tumor mice with cisplatin alone. After the treatment, the tumor suppressor rate of the transplanted tumor mice was observed: Ligustrazine group (35.58%), cisplatin group (40.41%), combined treatment group (62.48%), compared with the saline group. The tumor tumor inhibition rate in each group was significantly higher (P0.05). The necrosis rate of the tumor in the transplanted mice was (15.58 + 3.19), the tumor necrosis in the cisplatin group (24.64 + 11.96) and the combined treatment group (31.76 + 15.20) were higher than that of the normal saline group (9.37 + 1.36), and the difference was significant (P0.05). The combined treatment group was compared with the cisplatin group. The tumor necrosis rate and tumor necrosis rate of tumor mice increased significantly (P0.05), while cisplatin group was superior to the Ligustrazine group. It suggested that the combination of Ligustrazine and cisplatin was better than cisplatin.3. containing thrombin sensitive I type depolymer like metalloproteinase, vascular endothelial growth factor and microvascular density in Lewis lung cancer tissue. After all the tumor tissues were removed, VEGF was detected by immunohistochemistry. The results of ADAMTS1 showed that VEGF was positive in the four groups, compared with that of the normal saline group (56367.82 + 7441.12), the Ligustrazine group (28674.58 + 2331.40), the cisplatin group (23932.76 + 3151.59) and the combined treatment group (19183.99 + 1453.64), and the combined treatment of the group (19183.99 + 1453.64). The expression of the treatment group was the lowest, the difference was significant (P0.05).ADAMTS1 positive expression in the four groups, the Ligustrazine group (15475.27 + 2064.88), the cisplatin group (18382.79 + 2162.08) and the combined treatment group (26403.85 + 3293.36) was significantly higher than the control group (1646.74 + 212.96), the combined treatment group was the highest expression, the physiological saline group was the lowest, the difference was significant (P0.05). Eggs (P0.05). The results of white blot showed that the group of tetramethylpyrazine (0.57 + 0.02) and cisplatin group (0.79 + 0.01), the expression of (0.98 + 0.02) ADAMTS1 in the combined treatment group was significantly higher than that of the saline group (0.48 + 0.01), and the difference was significant (P0.05), while the expression of VEGF in the saline group (0.87 + 0.03) was the highest, and the expression of the combined treatment group (0.28 + 0.01) was the lowest. The results are basically consistent with the results of Western blot. Tetramethylpyrazine and cisplatin can reduce the expression of VEGF in lung adenocarcinoma and increase the expression of ADAMTS1. Ligustrazine Combined with cisplatin can further enhance its inhibition of VEGF expression, and promote the expression of ADAMTS1 in.4. microvessel density count by immunohistochemical method. The vascular density index (CD105), the tumor vessels were observed under the optical microscope, the count of microvessel density (MVD) was counted by the Weidner method. 3 experts in the pathology department were asked to observe 5 high times of visual field independently, and the average value was calculated. The results showed that the expression of the normal saline group was the highest (4.9 * 104 + 7.3 x 103), and the expression of the combined treatment group was the lowest (1.4). The morphology and vascular structure of the tumor cells were observed under transmission electron microscope (104 + 6.2 x 103). The results of transmission electron microscopy showed that the tumor cells in the saline group were densely distributed, the nucleolus were large and obvious, the karyotype was irregular, the mitochondria and the rough endoplasmic reticulum were abundant, and the apoptotic cells were found. The Ligustrazine group showed that some tumor cells were fatty degeneration and cell. The plasma lipid droplets increased, formed incomplete cell membrane, mitochondria vacuolation, necrotic cells and fragments, and organelles decreased. The distribution of tumor cells in cisplatin group and combined group was rare, the mitochondria swelling in the cytoplasm of some cells, more cell fragments, common apoptotic tumor cells, and occasional apoptotic bodies formed. To sum up, Lewis lung adenocarcinoma cells The survival state, body weight, tumor volume, tumor weight, vascular ultrastructure, changes of tumor cells, angiogenic factors and tumor suppressor rate were compared through experiments to observe the survival state, body weight, tumor volume, microvascular ultrastructure and angiogenesis of transplanted mice through experiment. The change of protein expression level and the comparison of tumor necrosis rate and tumor suppressor rate showed that Ligustrazine and cisplatin can improve the quality of survival and reduce the side effects. Ligustrazine can inhibit the growth of transplanted tumor in Lewis lung cancer mice, and have synergistic effect with cisplatin. Ligustrazine Combined with cisplatin can inhibit the expression of VEGF by inhibiting the combination of cisplatin and cisplatin. It can promote the expression of ADAMTS1, reduce angiogenesis and inhibit tumor growth.
【學(xué)位授予單位】：河北北方學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R734.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 張長(zhǎng)洪;張志林;張志華;張秀瓏;湯建華;劉開(kāi)楊;;川芎嗪聯(lián)合順鉑對(duì)Lewis肺腺癌小鼠抑制生長(zhǎng)的作用[J];中國(guó)臨床藥理學(xué)雜志;2015年11期

2 逯青麗;劉建;朱曉莉;徐文佳;;Expression of Nerve Growth Factor and Hypoxia Inducible Factor-1α and Its Correlation with Angiogenesis in Non-Small Cell Lung Cancer[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2014年03期

3 張璐;付毅;孔煒;;血管新生抑制因子研究進(jìn)展[J];轉(zhuǎn)化醫(yī)學(xué)研究(電子版);2013年03期

4 Ping Feng;Zhi-Lin Zhang;Zhi-Hua Zhang;Xiu-Long Zhang;Feng Xiang;Jian-Hua Tang;Bao-Li Xiang;;Effect of endostar combined with cisplatin on expression of VEGF and Sema3A of Lewis lung cancer rats[J];Asian Pacific Journal of Tropical Medicine;2013年01期

5 林淑儀;戴碧濤;;苦參堿和川芎嗪抑制白血病細(xì)胞侵襲轉(zhuǎn)移作用的實(shí)驗(yàn)研究[J];中國(guó)小兒血液與腫瘤雜志;2012年05期

6 ;Smac蛋白在HCC組織的表達(dá)及其與凋亡和增殖的關(guān)系(英文)[J];Chinese-German Journal of Clinical Oncology;2012年04期

7 袁玉國(guó);姚計(jì)方;;CD105在腫瘤抗血管治療中的研究與進(jìn)展[J];中國(guó)腫瘤外科雜志;2012年02期

8 王晶;鮑永霞;耿瑩;;地塞米松影響Lewis肺癌小鼠移植瘤生長(zhǎng)及微血管生成的研究[J];中國(guó)癌癥雜志;2012年01期

9 于利利;王澤華;;Effects of Livin Gene RNA Interference on Apoptosis of Cervical Cancer Hela Cells and Enhanced Sensitivity to Cisplatin[J];Journal of Huazhong University of Science and Technology(Medical Sciences);2009年05期

10 閆華超;李林尉;;抗腫瘤藥物誘導(dǎo)腫瘤細(xì)胞凋亡機(jī)制的研究進(jìn)展[J];聊城大學(xué)學(xué)報(bào)(自然科學(xué)版);2009年03期

相關(guān)博士學(xué)位論文 前1條

1 張會(huì)軍;人小細(xì)胞肺癌多藥耐藥細(xì)胞系H446/VP的建立及其耐藥機(jī)制與逆轉(zhuǎn)相關(guān)研究[D];河北醫(yī)科大學(xué);2004年

，

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