Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Malaysia.
Cancer Cell Int. 2012 Aug 1;12(1):35. doi: 10.1186/1475-2867-12-35.
Cisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. One of the candidates for anticancer virotherapy is the Newcastle disease virus (NDV). Even though NDV's oncolytic properties in various cancer cells have been widely reported, information regarding its effects on cisplatin resistant cancer cells is still limited. Therefore, we tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line.
Cisplatin-resistant cell line (MCF7-CR) was developed from the MCF7 human breast adenocarcinoma cell line by performing a seven-cyclic exposure to cisplatin. Following NDV infection, fluorescence-activated cell sorting (FACS) analysis and immunoblotting were used to measure cell viability and viral protein expression, respectively. Production of virus progeny was then assessed by using the plaque assay technique.
Infection of a mass population of the MCF7-CR with NDV resulted in 50% killing in the first 12 hours post-infection (hpi), comparable to the parental MCF7. From 12 hpi onwards, the remaining MCF7-CR became less susceptible to NDV killing. This reduced susceptibility led to increased viral protein synthesis and virus progeny production. The reduction was also associated with a prolonged cell survival via stabilization of the survivin protein.
Our findings showed for the first time, the involvement of survivin in the reduction of NDV-induced oncolysis in a subpopulation of cisplatin-resistant cells. This information will be important towards improving the efficacy of NDV as an anticancer agent in drug resistant cancers.
顺铂耐药是癌症治疗中的一个严重问题。为了克服这个问题，人们正在探索替代方法，包括病毒疗法。抗癌病毒疗法的候选者之一是纽卡斯尔病病毒（NDV）。尽管 NDV 在各种癌细胞中的溶瘤特性已被广泛报道，但关于其对顺铂耐药癌细胞的影响的信息仍然有限。因此，我们测试了一种 NDV 株（命名为 AF2240）在顺铂耐药乳腺癌细胞系中的溶瘤疗效。
通过对顺铂进行七轮暴露，从 MCF7 人乳腺腺癌细胞系中开发出顺铂耐药细胞系（MCF7-CR）。NDV 感染后，使用荧光激活细胞分选（FACS）分析和免疫印迹分别测量细胞活力和病毒蛋白表达。然后使用噬斑测定技术评估病毒产物的产生。
NDV 对 MCF7-CR 大量细胞群的感染导致感染后 12 小时（hpi）时 50%的细胞死亡，与亲本 MCF7 相当。从 12 hpi 开始，剩余的 MCF7-CR 对 NDV 杀伤的敏感性降低。这种敏感性降低导致病毒蛋白合成和病毒产物产生增加。减少还与通过稳定生存素蛋白延长细胞存活时间有关。
我们的研究结果首次表明，survivin 参与了亚群顺铂耐药细胞中 NDV 诱导的溶瘤作用的降低。这些信息对于提高 NDV 作为耐药性癌症中抗癌剂的疗效非常重要。
