Protein kinase C β inhibits autophagy and sensitizes cervical cancer Hela cells to cisplatin.

Na Li,Wei Zhang

doi:10.1042/bsr20160445

Abstract

Recently, autophagy has been indicated to play an essential role in various biological events, such as the response of cervical cancer cells to chemotherapy. However, the exact signalling mechanism that regulates autophagy during chemotherapy remains unclear. In the present study, we investigated the regulation by cisplatin on protein kinase C β (PKC β), on B-cell lymphoma 2 (Bcl-2) and on apoptosis in cervical cancer Hela cells. And then we examined the regulation by cisplatin on autophagy and the role of autophagy on the chemotherapy in Hela cells. In addition, the regulation of the PKC β on the autophagy was also investigated. Our results indicated that cisplatin promoted PKC β in Hela cells. The PKC β inhibitor reduced the cisplatin-induced apoptosis, whereas increased the cisplatin-induced autophagy in Hela cells. On the other side, the PKC β overexpression aggravated the cisplatin-induced apoptosis, whereas down-regulated the cisplatin-induced autophagy. Taken together, our study firstly recognized the involvement of PKC β in the cytotoxicity of cisplatin via inhibiting autophagy in cervical cancer cells. We propose that PKC β would sensitize cervical cancer cells to chemotherapy via reducing the chemotherapy induced autophagy in cancer cells.

Highlights

Cisplatin is an effective chemotherapeutic agent that is widely applied in treating solid tumours such as bladder, head and neck, lung, ovarian and testicular cancers [1]
We investigated the regulation by cisplatin on protein kinase C β (PKC β), on B-cell lymphoma 2 (Bcl-2) and on apoptosis in cervical cancer Hela cells, examined the regulation by cisplatin on autophagy and the role of autophagy on the chemotherapy and investigated the regulation of the protein kinase C (PKC) β on the autophagy
The expressions of PKC β, Bcl-2, p-PKC β, and internal control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in transfected cells were determined with western blotting (WB)

Summary

Introduction

Cisplatin is an effective chemotherapeutic agent that is widely applied in treating solid tumours such as bladder, head and neck, lung, ovarian and testicular cancers [1]. After WB analysis of each protein with the internal control GAPDH (Figure 1D), we found that single treatment of 20 μM of cisplatin induced the lowest Bcl-2 level and the highest p-PKC β level in treated Hela cells.

Results

Conclusion