Staurosporine alleviates cisplatin chemoresistance in human cancer cell models by suppressing the induction of SQSTM1/p62

Cancer is one of the leading causes of mortality worldwide. Platinum-based chemotherapeutic agents such as cisplatin are the first line of treatment for many types of cancers. However, the development of cisplatin resistance after prolonged treatment is a common cause of cancer recurrence. In the present study, we investigated an approach designed to overcome resistance to cisplatin involving co-treatment with a second chemotherapeutic agent, staurosporine, and examined the role of sequestosome 1 (SQSTM1/p62) in enhancing cellular sensitivity to cisplatin. We utilized experimental models of three different cancers comprising cell lines derived from colon, breast, and ovarian tumors and investigated cell proliferation, morphology and p62 levels after treatment with cisplatin, staurosporine, or a combination of the two. Western blot analysis showed that cisplatin treatment resulted in elevation of p62 levels when compared to the corresponding control cells. Conversely, treatment with staurosporine resulted in a marked reduction in p62 levels in all three cell types and abrogated the cisplatin-induced upregulation of p62. These results suggest that staurosporine could sensitize cancer cells to cisplatin via a mechanism involving downregulation of p62.