PKC伪 inhibited apoptosis by decreasing the activity of JNK in MCF-7/ADR cells
- 作者：Na Wang ; Zhihua Li ; Fen Tian ; Ying Feng ; Jintao Huang ; Chaohong Li ; lichaohongzq@yahoo.com ; Fukang Xie ; frankxie2000@yahoo.com
- 关键词：PKC ; protein kinase C ; JNK ; c-Jun NH2-terminal kinase ; MDR ; multidrug resistant ; TAM ; tamoxifen ; DCC-FBS ; fatal bovine serum stripped with dextrin-coated charcoal ; SP ; sp600125 ; Go ; Go6976
- 刊名：Experimental and Toxicologic Pathology
- 出版年：2012
- 期刊代码：128_09402993
- 类别：med
- 出版时间：July, 2012
- 卷：64
- 期：5
- 页码：459-464
- 文件大小：961 K
摘要
The development of multidrug resistance (MDR) in breast cancer patients is a serious therapeutic problem. The role of signal transduction in the development of MDR has drawn intensive attention recently. In this study, the role of c-Jun N-terminal kinase (JNK) pathway in MDR, specifically regulated by PKC伪, was investigated in MCF-7/ADR cells. MTT, DNA ladder and flow cytometry were used to detect cell growth inhibition or apoptosis while Western blot was used to detect the activation of proteins. Compared with MCF-7 cells, the cell growth inhibition and apoptosis induced by tamoxifen (TAM) could not be detected in MCF-7/ADR cells, but the expression of PKC伪 in MCF-7/ADR cells was higher. And, Western blot results showed that JNK was activated by TAM in MCF-7 cells while not in MCF-7/ADR cells, even at very high doses. In addition, sp600125, the inhibitor of JNK, decreased the percentage of apoptosis induced by TAM in MCF-7 cells. These data showed that PKC伪 and JNK were key regulators in the apoptosis of MCF-7/ADR cells. Furthermore, PKC伪 being the upstream of JNK in inhibiting apoptosis was suggested by using Go6976, the specific PKC伪 inhibitor, in the presence or absence of sp600125. This study highlighted an important signaling pathway involved in MDR regulated by PKC伪 in MCF-7/ADR breast cancer cells and implied that JNK might be an important downstream target of PKC伪 in this cellular context.