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卡非佐米聯(lián)合米托坦對(duì)人腎上腺皮質(zhì)癌細(xì)胞H295R、SW13增殖及細(xì)胞周期的影響

發(fā)布時(shí)間:2018-08-14 17:54
【摘要】:目的探討卡非佐米聯(lián)合米托坦對(duì)人腎上腺皮質(zhì)癌(ACC)細(xì)胞H295R、SW13增殖及細(xì)胞周期的影響。方法體外培養(yǎng)人ACC細(xì)胞H295R、SW13,采用MTT法確定米托坦作用H295R、SW13細(xì)胞48 h時(shí)的半數(shù)有效抑制濃度(IC_(50))值分別為18.42、62.37μmol/L,卡非佐米分別為3.86、11.62μmol/L。將兩種對(duì)數(shù)生長(zhǎng)期細(xì)胞隨機(jī)分為對(duì)照組、卡非佐米組、米托坦組及序貫給藥的卡非佐米→米托坦組、卡非佐米+米托坦組、米托坦→卡非佐米組,給藥濃度分別為兩種藥物IC_(50)值的1/8、1/4、1/2、1、2倍,檢測(cè)各濃度干預(yù)48 h時(shí)各組細(xì)胞增殖抑制率。根據(jù)Chou-Talaly公式計(jì)算IC_(50)及2倍IC_(50)作用下兩種藥物序貫給藥時(shí)的聯(lián)合指數(shù)(CI)。將兩種對(duì)數(shù)生長(zhǎng)期細(xì)胞隨機(jī)分為對(duì)照組、米托坦單藥組(25、50μmol/L)、卡非佐米單藥組(1μmol/L)、卡非佐米(1μmol/L)→米托坦(25、50μmol/L)組,藥物干預(yù)48 h時(shí)檢測(cè)細(xì)胞增殖抑制率。將兩種對(duì)數(shù)生長(zhǎng)期細(xì)胞隨機(jī)分為空白組、米托坦組、卡非佐米組、卡非佐米→米托坦組,后三組以IC_(50)藥物濃度干預(yù)96 h,采用流式細(xì)胞儀檢測(cè)細(xì)胞周期。結(jié)果 H295R及SW13細(xì)胞在IC_(50)及2倍IC_(50)濃度下,卡非佐米→米托坦組細(xì)胞增殖抑制率均高于米托坦→卡非佐米組及卡非佐米+米托坦組,米托坦→卡非佐米組均高于卡非佐米+米托坦組,組間比較P均0.05。H295R和SW13細(xì)胞在米托坦、卡非佐米IC_(50)及2倍IC_(50)濃度條件下,卡非佐米→米托坦組和米托坦+卡非佐米組中兩藥的CI值均1,且卡非佐米→米托坦組兩藥的CI值均小于米托坦+卡非佐米組(P均0.05);米托坦→卡非佐米組中兩藥的CI值均1,且均高于卡非佐米→米托坦組和米托坦+卡非佐米組(P均0.05)。1μmol/L卡非佐米與25、50μmol/L米托坦聯(lián)合的卡非佐米→米托坦組H295R及SW13增殖抑制率分別高于25、50μmol/L米托坦組(P均0.05)。四組G1、G2/M、S期細(xì)胞百分比比較差異均無(wú)統(tǒng)計(jì)學(xué)意義(P均0.05)。結(jié)論卡非佐米聯(lián)合米托坦對(duì)ACC細(xì)胞存在序貫依賴性的協(xié)同抑制細(xì)胞增殖作用,給予卡非佐米后給予米托坦的抗增殖作用最佳,但兩藥聯(lián)合對(duì)細(xì)胞周期無(wú)明顯影響。
[Abstract]:Objective to investigate the effects of Carfezomi combined with Mitotam on the proliferation and cell cycle of human adrenocortical carcinoma (ACC) cell line H295 RN SW13. Methods Human ACC cells were cultured in vitro. MTT assay was used to determine the median effective inhibitory concentrations (IC50) of H295RNSW13 cells at 48 h after treatment with Mitotam (18.42 渭 mol / L) and carbofezomil (3.8611.62 渭 mol / L), respectively. Two kinds of logarithmic growth cells were randomly divided into control group, Carfezomi group, mitosartan group and sequential administration of Carfezomidone group, Carfezomitartan group, mitosomide group, and mitosomide group. The concentration of IC50 was 1 / 8 / 1 / 4 / 2 / 1 / 2 of IC50, respectively. The cell proliferation inhibition rate of each group was measured at 48 h after each concentration was interfered. Calculation of the combined index (CI). For sequential administration of two drugs under the action of IC _ (50) and 2 times IC _ (50) according to Chou-Talaly formula Two kinds of logarithmic growth cells were randomly divided into control group, mitotam group (2550 渭 mol/L), captopamil monotherapy group (1 渭 mol/L) and carfezomi group (1 渭 mol/L). The inhibitory rate of cell proliferation was measured at 48 h after drug intervention. Two kinds of logarithmic growth cells were randomly divided into three groups: the control group, the Mitotam group and the carbazolitine group. The latter three groups were treated with IC50 for 96 h, and the cell cycle was measured by flow cytometry. Results at the concentration of IC50 and 2 times IC50, the cell proliferation inhibition rate in the group of Cafizolmitam and SW13 was higher than that in the group of mitotam and the group of caprizomitosamitone, and the inhibition rate of cell proliferation in the two groups was higher than that in the group of mitotazolidone and the group of mifetotazolam. The P average of 0.05.H295R and SW13 cells in the mitotam group was higher than that in the captozotocin group at the concentration of mitotam, captopamil IC _ (50) and 2 times IC50, and the difference between the two groups was observed. The CI values of the two drugs in the two groups were 1 and 1, respectively, and the CI values of the two drugs were lower than those of the mitotancaptopamil group (P 0.05), and the CI values of the two drugs were lower than those of the mitotam captopamil group (P 0.05), and the CI values of the two drugs were lower than those of the mitotancaptopamil group (P 0.05). The CI values were 1, and were higher than those in the two groups (P < 0. 05). The inhibition rates of H295R and SW13 proliferation in the mitotazolam group were higher than those in the two groups (P < 0. 05). The inhibitory rates of H295R and SW13 in the mitotazolam group were significantly higher than those in the 2 550 渭 mol/L mittopam group (P < 0. 05). There was no significant difference in the percentage of G _ 1 G _ 2 / M _ 2 / M _ 2 phase cells among the four groups (P 0.05). Conclusion Carfezomi combined with mitotam has a sequential synergistic inhibitory effect on the proliferation of ACC cells. The antiproliferative effect of the combination of the two drugs is the best, but the combination of the two drugs has no obvious effect on the cell cycle.
【作者單位】: 廣西醫(yī)科大學(xué)第一附屬醫(yī)院;
【基金】:國(guó)家自然科學(xué)基金資助項(xiàng)目(81060220)
【分類號(hào)】:R736.6

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