In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 4306-4306
Abstract:
Hyperthermia therapy is one of the most widely studied non-surgical methods for breast tumors, which eliminates tumor by inducing acute stress on tumor cells. However, it has been extensively known that the viability of the tumor cells is highly influenced by the applied temperature. Insufficient thermal stress during hyperthermia treatments may alter tumor microenvironment by promoting epithelial to mesenchymal-like transition (EMT) and as a result, enhancing the outgrowth of residual tumor cells. Therefore, cells that have survived from sublethal thermal stress and experienced EMT may cause substantial clinical problems. In this case, hyperthermia requires additional therapy in order to promote cell death of more invasive tumor cells that have resisted to the thermal stimulus. In this study, we confirmed that the co-treatment of chemotherapy with hyperthermia may overcome the phenotypical transition caused by insufficient heat treatment. After exposing breast cancer cells (MCF-7) into two different temperature conditions (42°C and 47°C) for an hour, we have verified that 10.51 ± 1.71% and 18.27 ± 10.66% of cells experienced apoptosis or necrosis when the cells were exposed to 42°C and 47°C, respectively. At the same time, cancer cells showed higher invasiveness, spear-like morphology, and enhanced migratory behaviors as the exposed temperature increases, which is mainly shown among the cells that have experienced EMT. Further western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR) using mesenchymal marker (vimentin) and epithelial marker (E-cadherin) also support that the mesenchymal-like phenotype has been highly increased on the cells that have resisted to the thermal stress. However, when chemotherapy was conducted after the heat treatment, cell viability was highly reduced. Paclitaxel (11.7 nM), cisplatin (3.3 μM), and combination of two anticancer drugs were treated for 24 hours on the cells that have been exposed to different temperatures, respectively. As a result, death rate of tumor cells has increased from 11.31 to 66.69%. Especially, when paclitaxel and cisplatin were co-treated, the death rate was up to 73.75 ± 4.37% after cells were exposed to 47°C. In conclusion, cancer cells that have survived from insufficient hyperthermia showed high potential to promote metastasis or recurrence but additional chemotherapy can successfully reduce the side effects induced by insufficient hyperthermia treatment. Citation Format: Tae Hee Lee, Jiyoon Bu, Byoung Hyuck Kim, Young Jun Kim, Yoon-Tae Kang, Jung Eun Moon, Young-Ho Cho. Combined effects of chemotherapy to reduce metastasis caused by insufficient hyperthermia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4306. doi:10.1158/1538-7445.AM2017-4306
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-4306
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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