Ad.mda-7/IL-24对卵巢癌耐药细胞株生长及耐药的影响

Effects of Adenoviral-mediated mda-7/IL-24 Gene Infection on the Growth and Drug-resistance of Drug-resistant Ovarian Cancer Cell Lines

目的探讨抑癌基因mda-7/IL-24对卵巢癌耐药细胞株OVCAR-3、OVCAR-8/TR生长和耐药性的影响。方法以前期研究成功构建的mda-7/IL-24基因重组腺病毒载体Ad.mda-7/IL-24感染OVCAR-3、OVCAR-8/TR两种卵巢癌耐药细胞株,Western blot检测MDA-7/IL-24蛋白的表达,MTT法检测细胞感染后的生长增殖情况,以及对顺氯氨铂(DDP)、阿霉素(ADM)、5-氟尿嘧啶(5-FU)、泰素(Taxol)4种化疗药物敏感性的变化。结果OVCAR-3、OVCAR-8/TR细胞在病毒感染量为10μL时,均达到100%感染率;细胞感染后可成功表达MDA-7/IL-24蛋白;Ad.mda-7/IL-24感染OVCAR-3、OVCAR-8/TR后细胞生长抑制明显,第5d细胞生存率分别降至10.5%和35.8%;感染后两种细胞的泰素药敏分别约为未感染前的2.76和1.52倍,OVCAR-3细胞对ADM和5-FU药敏分别约为未感染前的1.6和3.01倍。结论mda-7/IL-24基因对卵巢癌耐药细胞有生长抑制作用,同时可能逆转肿瘤细胞对泰素的耐药性。

Objective To study the effects of tumor suppressor gene mda-7/IL-24 on the growth and drugresistance of two drug-resistant ovarian cancer cell lines OVCAR-3, OVCAR-8/TR. Methods Adenoviral- mediated mda-7/IL-24 （Ad. mda-7/IL-24） was constructed in our previous study, and then applied to infect two cell lines. Western blot analysis was used to detect the expression of MDA-7/IL-24 protein. The cell viability and resistance against four chemotherapeutic drugs, including DDP, ADM, 5-FU and Taxol, were examined with methyl thiazolyl tetrazolium （MTT） rapid photocolorimetric assay. Results All OVCAR-8/TR and OVCAR-3 cells were infected under the condition that Ad. mda-7/IL-24 was 10μL, and successfully infected cells could express the MDA-7/IL-24 protein. OVCAR-3 and OVCAR-8/TR cell growth were significantly inhibited after cells infected by Ad. mda-7/IL-24. The cell viability decreased to 10. 5% and 35.8% respectively in the fifth day. The sensitivity of infected OVCAR-3 or OVCAR-8/TR to Taxol was increased up to 2. 76 or 1. 52 times, as compared with the control. The infected OVCAR-3 cells also had higher sensitivity to ADM and 5-FU, which digitally increased respectively 1. 6 and 3. 01 times when compared to the sensitivities before cells infected. Conclusion The mda-7/IL-24 gene shows cancer growth inhibition on drug-resistance ovarian caner cell lines. Ad. mda-7/IL-24 infecting cell may have the capability of reversing the resistance of tumor cell against Taxol.