目的 探討生存素(survivin)反義核酸(anti-pcDNA3-svv)對胃癌細胞SGC7901的凋亡誘導,對泰索帝的化療增敏作用及降低多藥耐藥基因-1(MDR-1)表達的作用。
方法 采用脂質(zhì)體法轉(zhuǎn)染SGC7901細胞,并篩選陽性克隆,Western blot檢測survivin蛋白的表達,RT-PCR檢測 MDR-1 mRNA的表達,透射電鏡觀察轉(zhuǎn)染后對SGC7901細胞的凋亡誘導作用,MTT法檢測轉(zhuǎn)染細胞對泰索帝的敏感性。
結(jié)果 survivin蛋白的表達在重組質(zhì)粒組比空質(zhì)粒組和空白對照組明顯降低(P<0.05),重組質(zhì)粒組MDR-1 mRNA表達也較其他2組明顯降低(P<0.01); 透射電鏡下可見重組質(zhì)粒組細胞呈凋亡晚期變化,其MDR指數(shù)為0.196±0.013,明顯低于空質(zhì)粒組的2.958±0.024和空白對照組的3.126±0.019(P<0.01); 重組質(zhì)粒組對泰索帝的IC50值為(16.7±1.98) ng/ml,也明顯低于空質(zhì)粒組的(49.9±1.21) ng/ml和空白對照組的(55.7±1.89) ng/ml(P<0.01)。
結(jié)論 survivin反義核酸可誘導SGC7901細胞凋亡,增強泰索帝化療敏感性,可能逆轉(zhuǎn)耐藥。
引用本文: 陳曦海,張豈凡,馬榮. 反義survivin誘導胃癌SGC7901細胞凋亡及逆轉(zhuǎn)耐藥的研究. 中國普外基礎(chǔ)與臨床雜志, 2007, 14(1): 63-67. doi: 復制
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- 1. 姚學權(quán), 劉福坤, 祁曉萍, 等. 胃腺癌組織survivin基因的表達與細胞增殖及凋亡的相關(guān)性研究 [J]. 中華外科雜志, 2004; 42(3)∶145.
- 2. Trieb K, Lehner R, Stulnig T, et al. Survivin expression in human osteosarcoma is a marker for survival [J]. Eur J Surg Oncol, 2003; 29(4)∶379.
- 3. Chen LT, Liu TW, Wu CW, et al. A phase Ⅰ study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer [J]. Oncology, 2002; 63(3)∶239.
- 4. Suzuki T, Yoshida K, Tanabe K, et al. Three advanced gastric cancer patients successfully treated by combination therapy of docetaxel and TS-1 [J]. Gan To Kagaku Ryoho, 2005; 32(4)∶509.
- 5. Shin S, Sung BJ, Cho YS, et al. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7 [J]. Biochemistry, 2001; 40(4)∶1117.
- 6. Giodini A, Kallio MJ, Wall NR, et al. Regulation of microtubule stability and mitotic progression by survivin [J]. Cancer Res, 2002; 62(9)∶2462.
- 7. Lens SM, Wolthuis RM, Klompmaker R, et al. Survivin is required for a sustained spindle checkpoint arrest in response to lack of tension [J]. EMBO J, 2003; 22(12)∶2934.
- 8. Zaffaroni N, Daidone MG. Survivin expression and resistance to anticancer treatments: perspectives for new therapeutic interventions [J]. Drug Resist Updat, 2002; 5(2)∶65.
- 9. Bali P, Pranpat M, Swaby R, et al. Activity of suberoylanilide hydroxamic acid against human breast cancer cells with amplification of her-2 [J]. Clin Cancer Res, 2005; 11(17)∶6382.
- 10. Notarbartolo M, Cervello M, Dusonchet L, et al. Resistance to diverse apoptotic triggers in multidrug resistant HL60 cells and its possible relationship to the expression of P-glycoprotein, Fas and of the novel anti-apoptosis factors IAP (inhibitory of apoptosis proteins) [J]. Cancer Lett, 2002; 180(1)∶91.
- 11. 韓艷秋, 袁家穎, 石永進, 等. 小檗胺逆轉(zhuǎn)K562/A02細胞耐藥性及其機制 [J]. 中國實驗血液學雜志, 2003; 11(6)∶604.