【摘要】：放射治療是惡性腫瘤治療過程中重要的局部治療手段。但常規(guī)射線在輻照過程中存在著諸多天然缺陷,其深度劑量分布呈指數(shù)衰減形式,在抵達(dá)腫瘤區(qū)域?qū)δ[瘤細(xì)胞造成殺傷的同時,對腫瘤周圍組織也有一定損傷。臨床上為避免輻照對正常組織的輻照損傷,通常會降低輻照總劑量。近期研究表明,常規(guī)射線在輻照劑量不足時,可導(dǎo)致惡性腫瘤的侵襲能力增強(qiáng)。所以人們便積極地尋求出一種更優(yōu)越的放療用射線——重離子束。重離子是一種高LET(Linear energy transfer)射線,其在射程末端擁有一個陡峭的高劑量Bragg峰,其可最大限度地殺傷腫瘤細(xì)胞；具有高的相對生物學(xué)效應(yīng),與常規(guī)射線相比,造成腫瘤細(xì)胞的損傷更嚴(yán)重。重離子束也被譽(yù)為是21世紀(jì)最為理想的放療射線。 腫瘤向周圍組織的侵襲,是腫瘤轉(zhuǎn)移的最初始階段,也是一種多因子參與的復(fù)雜過程。在這一過程中,基質(zhì)金屬蛋白酶(MMPs)是人體內(nèi)最主要的蛋白水解酶,對癌細(xì)胞的粘附和侵襲均發(fā)揮著重要的作用�；|(zhì)金屬蛋白酶在許多人類的癌組織中均有表達(dá)和活性的增強(qiáng),其中基質(zhì)金屬蛋白酶-2和基質(zhì)金屬蛋白酶-9(MMP-2, MMP-9)是腫瘤侵襲過程中關(guān)鍵因子。MMP-2和MMP-9是可以分解細(xì)胞基底膜上的Ⅳ型膠原蛋白和彈性蛋白成份,使腫瘤細(xì)胞突破基底膜的能力增強(qiáng),從而促進(jìn)腫瘤細(xì)胞向周圍組織侵襲。 本實(shí)驗(yàn)以人舌鱗癌細(xì)胞株Tca8113為主要研究對象,使用不同劑量的X線和12C6+重離子束對其進(jìn)行輻照,采用Western-blot法觀察MMP-2和MMP-9在舌鱗癌細(xì)胞中表達(dá)的變化,反映兩種輻照對于腫瘤侵襲能力的影響。結(jié)果如下： 和空白對照組相比,使用1GyX射線在輻照后12h、24h和48h, MMP-2的表達(dá)含量均有所上調(diào)(p0.05),其表達(dá)含量于24h時達(dá)到頂峰(p0.01),在48h時,MMP-2的表達(dá)有所下調(diào)；4Gy X射線輻照后的細(xì)胞中MMP-2在各個時間點(diǎn)的表達(dá)水平雖有所減少,但并不具備統(tǒng)計(jì)學(xué)差異(p0.05)。1Gy和4Gy X射線進(jìn)行輻照后,細(xì)胞中MMP-9的表達(dá)也未出現(xiàn)明顯改變(p0.05)。 1Gy重離子束對舌鱗癌細(xì)胞進(jìn)行輻照后,MMP-2于12h時出現(xiàn)表達(dá)含量的升高(p0.05),但其表達(dá)水平與24h和48h時又出現(xiàn)了明顯的下降(p0.05)。低劑量重離子束對舌鱗癌細(xì)胞中MMP-9的表達(dá)沒有明顯影響(p0.05)；在使用4Gy重離子束對腫瘤細(xì)胞進(jìn)行輻照后,MMP-2和MMP-9的表達(dá)有著明顯降低(p0.05)。 通過以上實(shí)驗(yàn)結(jié)果,可以得出：低劑量的X射線可增進(jìn)舌鱗癌細(xì)胞Tca8113細(xì)胞的體外侵襲能力；高劑量的X射線對于舌鱗癌細(xì)胞Tca8113的侵襲能力并沒有明顯影響。低劑量的重離子束輻照對于舌鱗癌細(xì)胞Tca8113的侵襲能力沒有影響；高劑量重離子束可明顯抑制舌鱗癌的體外侵襲能力。和X射線相比,重離子束在抑制舌鱗癌體外侵襲方面具有更高的相對生物學(xué)效率。
[Abstract]:Radiotherapy is an important local treatment method in the treatment of malignant tumor. However, there are many natural defects in the irradiation process of conventional radiation, whose depth dose distribution is exponentially attenuated. When reaching the tumor area to kill the tumor cells, it also has some damage to the surrounding tissues of the tumor. In order to avoid radiation damage to normal tissues, the total dose of irradiation is usually reduced. Recent studies have shown that conventional radiation can enhance the invasiveness of malignant tumors when irradiation dose is insufficient. So people are actively looking for a better radiation-heavy ion beam. Heavy ions are high LET (Linear energy transfer) rays with a steep high dose Bragg peak at the end of the range, which can kill tumor cells to the maximum extent. It has high relative biological effect, and the damage of tumor cells is more serious than conventional radiation. Heavy ion beam is also regarded as the most ideal radiation in the 21 st century. Invasion of tumor to surrounding tissues is the initial stage of tumor metastasis and a complex process involving multiple factors. In this process, matrix metalloproteinase (MMPs) is the most important proteolytic enzyme in human body, and plays an important role in adhesion and invasion of cancer cells. The expression and activity of matrix metalloproteinase (MMP-2) and matrix metalloproteinase-9 (MMP-2,) are increased in many human carcinomas, including matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-2,). MMP-9) is a key factor in the process of tumor invasion. MMP-2 and MMP-9 can decompose the type 鈪，

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