title: The Zuo Jin Wan Formula Induces Mitochondrial Apoptosis of Cisplatin-Resistant Gastric Cancer Cells via Cofilin-1.
abstract: 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.
authors.affiliation: Central Laboratory and Department of Clinical Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China; Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Tang
authors.affiliation: Central Laboratory and Department of Clinical Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Central Laboratory and Department of Clinical Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Central Laboratory and Department of Clinical Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Shi
authors.affiliation: Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Lv
authors.affiliation: Basic Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hong-Chang
authors.identifier: 0000-0003-1632-1346
authors.initials: HC
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Pei-Hao
authors.identifier: 0000-0002-7443-4018
authors.initials: PH
authors.lastname: Yin