Combination therapy with BH3 mimetic and hyperthermia tends to be more effective on anti-melanoma treatment

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.06.010· OSTI ID:23105709

Shi, Zhen ^[1]; Lan, Bin; Peng, Baowei ^[2]; Wang, Xuefeng ^[1]; Zhang, Ganggang ^[2]; Li, Xiaohu ^[3]; Guo, Fang ^[1]

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1. University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049 (China)
2. Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Rd, Minhang, Shanghai, 200240 (China)
3. Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Pudong, Shanghai, 201210 (China)

Highlights: • The anti-melanoma ability of ch282-5 is synergistically amplified by hyperthermia. • Combination therapy with ch282-5 and hyperthermia activates pro-apoptotic signaling and inhibits pro-survival signaling. • Ch282-5 combining with microwave hyperthermia remits pulmonary colonization of melanoma cells. 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.

• OSTI ID: 23105709
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 503; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
HYPERTHERMIA
MELANOMAS
MICROWAVE RADIATION
PROTEINS