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

Abstract

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.

• Authors: Zhen Shi, Bin Lan, Baowei Peng, Xuefeng Wang, Ganggang Zhang, Xiaohu Li, Fang Guo
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 503 Issue 1 Pg. 249-256 (09 03 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 29885833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• BH3 Interacting Domain Death Agonist Protein
• Inhibitor of Apoptosis Proteins
• gossypolone
• Gossypol

Topics

• Animals
• Apoptosis (drug effects)
• BH3 Interacting Domain Death Agonist Protein (antagonists & inhibitors)
• Biomimetics
• Cell Line, Tumor
• Cell Movement (drug effects)
• Combined Modality Therapy
• Gossypol (analogs & derivatives, pharmacology)
• Humans
• Hyperthermia, Induced
• Inhibitor of Apoptosis Proteins (antagonists & inhibitors)
• Lung Neoplasms (prevention & control, secondary)
• Male
• Melanoma (metabolism, pathology, therapy)
• Melanoma, Experimental (metabolism, pathology, therapy)
• Mice
• Mice, Inbred C57BL
• Microwaves (therapeutic use)
• Signal Transduction (drug effects)
• Skin Neoplasms (metabolism, pathology, therapy)