Reduced Newcastle disease virus-induced oncolysis in a subpopulation of cisplatin-resistant MCF7 cells is associated with survivin stabilization

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.Cisplatin cis-diaminedichloroplatinum(II), CDDP] is one of the widely used drugs to treat cancer patients. It was first discovered in 1969 [1] and has since been used to treat a variety of malignant tumors such as lung, ovarian, head and neck, bladder and testicular cancers [2]. Even though CDDP and other platinum complexes are not commonly used in the current therapy of breast cancers, they have recently been introduced into the clinical setting as an emerging new treatment modality [3,4]. The mode of action of this drug is believed to result from binding of its platinum molecule onto DNA of target cell. The incorporation of CDDP into DNA produces intrastrand and interstrand crosslink adducts [5,6]. The DNA-platinum adducts then prevent cells from undergoing DNA replication, prevent efficient RNA transcription and disrupting cell cycle which eve