Abstract
BackgroundCisplatin 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.MethodsCisplatin-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.ResultsInfection 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.ConclusionsOur 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.
Highlights
Cisplatin resistance is a serious problem in cancer treatment
Cisplatin (CDDP) resistance correlates with morphological changes in MCF7 cells MCF7 cell line was employed as a model to study Newcastle disease virus (NDV) oncolytic activity in CDDP-sensitive versus CDDPresistant breast cancer cells
During the CDDP treatment, surviving MCF7 cells showed an average of 2-fold increase in size compared to the control untreated MCF7 (Figure 1A)
Summary
Cisplatin resistance is a serious problem in cancer treatment. To overcome it, alternative approaches including virotherapy are being pursued. 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. We tested the oncolytic efficacy of a strain of NDV, designated as AF2240, in a cisplatin-resistant breast cancer cell line. 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 DNAplatinum adducts prevent cells from undergoing DNA replication, prevent efficient RNA transcription and disrupting cell cycle which eventually lead them to apoptosis [7,8]
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