Details

Autor(en) / Beteiligte

• Yin, Peihao
• Lv, Rong
• Shi, Xiao-jing
• Yu, Hui
• Sun, Jian
• Tang, Qing-Feng
• Wei, Hong-Chang
• Gincel, Dan

Titel

The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin-Resistant Gastric Cancer Cells via Cofilin-1

Ist Teil von

• Evidence-based complementary and alternative medicine, 2016-01, Vol.2016 (2016), p.1-14

Ort / Verlag

Cairo, Egypt: Hindawi Publishing Corporation

Erscheinungsjahr

2016

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy. Here we found that phosphorylated cofilin-1 (p-cofilin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901 and BGC823), and that DDP induced the dephosphorylation of p-cofilin-1 in both parent lines but not in the DDP-resistant lines. However, we noted that the traditional Chinese medicine formula Zuo Jin Wan (ZJW) could induce the dephosphorylation of p-cofilin-1 and promote cofilin-1 translocation from the cytoplasm into the mitochondria in both SGC7901/DDP and BGC823/DDP cells. This mitochondrial translocation of cofilin-1 was found to induce the conversion of filamentous actin to globular-actin, activate mitochondrial damage and calcium overloading, and induce the mitochondrial apoptosis pathway. We further observed that these effects of ZJW on DDP-resistant human gastric cancer cell lines could be reversed via transfection with cofilin-1-specific siRNA, or treatment with a PP1 and PP2A inhibitor. These results suggest that ZJW is an effective drug therapy for patients with DDP-resistant gastric cancer.