黑色素瘤
联合疗法
体内
细胞凋亡
癌症研究
热疗
PI3K/AKT/mTOR通路
医学
活力测定
体外
MAPK/ERK通路
药理学
化学
信号转导
生物
内科学
生物化学
生物技术
作者
Zhen Jun Shi,Bin Liu,Binbin Peng,Xuefeng Wang,Ganggang Zhang,Xiaohu Li,Fang Guo
标识
DOI:10.1016/j.bbrc.2018.06.010
摘要
Malignant melanoma has shown increased incidence and high mortality rate in the last three decades. In this study, we investigated whether combination therapy with ch282-5 (a novel BH3 mimetic) and microwave hyperthermia could display synergistic antitumor effects against melanoma. Our results indicated that combination therapy reduced the viability and proliferation of melanoma cells. Through inhibiting the expression of anti-apoptotic proteins of Bcl-2 and IAP family and activating MAPK proteins, combined hyperthermia enhanced ch282-5-induced apoptosis. Combination therapy also synergistically disturbed the mTOR/p70S6k signaling pathway, which is important for cell survival and migration. Moreover, our results showed that combination therapy remarkably suppressed melanoma cell migration in vitro and significantly reduced experimental pulmonary metastasis in vivo. In conclusion, our results indicate that combination therapy with ch282-5 and hyperthermia has synergistic antitumor effects and provides a possible therapeutic strategy for advanced melanoma.
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