Inhibitory action of cardiotoxin III on breast cancer MDA-MB-231 cell migration and invasion : Mechanisms of action

• Main Authors: Pei-Chien Tsai, 蔡沛倩
• Other Authors: Sodio Hsu
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/85041356772388982360

博士 === 高雄醫學大學 === 醫藥暨應用化學系博士班 === 105 === Metastasis causes a poor prognosis and high mortality rate of breast cancer patients. Because epithelial-mesenchymal transition (EMT) is the initial step for breast cancer metastasis, suppression of EMT might improve breast cancer therapy. Aberrant activation of Src-, EGF/EGFR-, HGF/c-Met-mediated downstream signaling pathways has been reported to contribute to progression, invasion, and malignant phenotype of breast cancer. Previous studies show that cardiotoxin III (CTX III) isolated from the Naja naja atra venom exhibits anti-cancer activities. Thus, in the present study, the inhibitory activity of CTX III on Src-, HGF/c-Met- and EGF/EGFR-induced EMT, metastasis and the associated signaling networks was investigated in breast cancer MDA-MB-231 cells. The data of the present study showed that CTX III treatment caused the morphologic changes of MDA-MB-231 cells from spindle-shaped to round appearance. CTX III attenuated the expression of EMT markers in EGF-/HGF-treated MDA-MB-231 cells through its suppressive effect on the EGF/EGFR and HGF/c-Met-induced activation of Src dependent FAK, p130Cas, paxillin, PI3K/Akt, and ERK signaling pathways. On the other hand, CTX III mitigated Src-, EGF/EGFR- and HGF/c-Met-elicited activation of PI3K/Akt and ERK1/2, and thus inhibited metastasis and invasion of MDA-MB-231 cells. Collectively, our data indicate that CTX III suppresses Src-, EGF/EGFR- and HGF/c-Met-induced EMT, metastasis, and invasion of breast cancer cells. These findings suggest that the signaling pathways inhibited by CTX III treatment are potential targets in treating breast cancer, and that the potential utility of CTX III as a structural template for developing protein drugs.