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Combined treatment with modulated electro-hyperthermia and an autophagy inhibitor effectively inhibit ovarian and cervical cancer growth

Authors
 Wookyeom Yang  ;  Gwan Hee Han  ;  Ha-Yeon Shin  ;  Eun-Ju Lee  ;  Hanbyoul Cho  ;  Doo Byung Chay   ;  Jae-Hoon Kim 
Citation
 INTERNATIONAL JOURNAL OF HYPERTHERMIA, Vol.36(1) : 9-20, 2019 
Journal Title
 INTERNATIONAL JOURNAL OF HYPERTHERMIA 
ISSN
 0265-6736 
Issue Date
2019
Keywords
Modulated electro-hyperthermia ; anti-cancer effects ;  autophagy inhibitor ;  cervical cancer ;  ovarian cancer
Abstract
PURPOSE: Modulated electro-hyperthermia (mEHT), known as oncothermia, is an anticancer therapy that induces radiofrequency thermal damage to the cancer tissues. This study aimed to evaluate the potential effectiveness of mEHT as a therapeutic tool in ovarian and cervical cancer. MATERIALS AND METHODS: We used both tumor-bearing mice and ovarian and cervical OVCAR-3, SK-OV-3, HeLa and SNU-17 cancer cell lines to investigate the effects of mEHT in vivo and in vitro, respectively, and determine whether it was enhanced by cotreatment with an autophagy inhibitor. RESULTS: We discovered that phosphorylation of p38, a stress-dependent kinase, was induced at the Thr180/Tyr182 residue in cancer cells exposed to mEHT. Apoptotic markers such as cleaved caspase-3 and poly-ADP ribose polymerase (PARP) were increased in OVCAR-3 and SNU-17 cells. Fluorescence-activated cell sorting (FACS) analysis showed a significant increase in the population of sub-G1 mEHT-exposed cells, which are dying and apoptotic cells. mEHT also reduced both weight and volume of xenograft tumors in mice transplanted with ovarian and cervical cancer cells and patient-derived cancer tissues. We determined that mEHT-induced cellular damage recovery was mediated by autophagy and, therefore, expectedly, cotreatment with mEHT and 3-methyladenine (3-MA), an autophagy inhibitor, more effectively inhibited cancer cell growth than individual treatment did. CONCLUSIONS: mEHT treatment alone was sufficient to inhibit cancer growth, while a combined treatment with mEHT and an autophagy inhibitor amplified this inhibition effect.
Full Text
https://www.tandfonline.com/doi/full/10.1080/02656736.2018.1528390
DOI
10.1080/02656736.2018.1528393
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jae Hoon(김재훈) ORCID logo https://orcid.org/0000-0001-6599-7065
Cho, Hanbyoul(조한별) ORCID logo https://orcid.org/0000-0002-6177-1648
Chay, Doo Byung(채두병) ORCID logo https://orcid.org/0000-0002-0648-4021
Han, Gwan Hee(한관희) ORCID logo https://orcid.org/0000-0001-5263-4855
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170203
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