Turkish Journal of Gastroenterology
Original Article

Cellular and Molecular Mechanism of Cell Proliferation in Human Gastric Cancer Drug-Resistant Cells After Hyperthermia and Cisplatin: Role of mRNAs and Long-Non-coding RNAs


Department of Surgery, Kerman University of Medical Sciences Faculty of Medicine, Kerman, Iran


Department of Internal Medicine, Mashhad University of Medical Sciences Faculty of Medicine, Mashhad, Iran


Department of Gastroenterology, Shangrao People’s Hospital, Jiangxi Province, China


Department of Traditional Chinese Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing City, China


Department of Pathology, Shangrao People’s Hospital, Jiangxi Province, China


Department of Neurosurgery, University Medical Center, Tuebingen, Germany

Turk J Gastroenterol 2022; 33: 377-386
DOI: 10.5152/tjg.2022.20845
Read: 272 Downloads: 98 Published: 01 May 2022

Background: Since thermo-chemotherapy was suggested as an effective treatment for gastric cancer, we aimed to evaluate the effects of hyperthermia combined with cisplatin (DDP) on the inhibition of human gastric cancer drug-resistant cells in vitro and explore its possible mechanisms.

Methods: SGC-7901/DDP cells were cultured and divided into control, cisplatin, hyperthermia, and hyperthermia combined with cispla- tin groups. Hyperthermia was done at 42°C, 44°C, 46°C, 48°C, and 50°C for 12 h, 24 h, 36 h; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay detected the proliferation of SGC-7901/DDP at different time and temperature, and the apoptotic rate of SGC-7901/DDP cells was evaluated by using Annexin staining assay. High-throughput Chromatin immunoprecipitation (ChIP)- seq was applied to test long non-coding RNA expression in SGC-7901/DDP cells. Then, real-time fluorescence quantitative polymerase chain reaction was used to verify the expression of long non-coding RNA in all groups.

Results: Double staining showed that hyperthermia combined with cisplatin increased the rate of early apoptosis of SGC-7901/DDP cells. Long non-coding RNA high-throughput ChIP-seq showed a significantly larger amount of long non-coding RNAs and mRNAs in the cells treated with hyperthermia combined cisplatin group in comparison with the control group. We observed that the upregulated mRNAs and long non-coding RNAs were highly related to immune system response and CD95 signaling pathway in nucleus, and down- regulated mRNAs and long non-coding RNA were highly related to Mammalian target of rapamycin (mTOR) and Tumor necrosis factor (TNF) receptor signaling pathway in cytoplasm.

Conclusion: Hyperthermia combined with cisplatin reversed the expression of a large number of mRNAs and long non-coding RNAs in human gastric cancer drug-resistant cells. The molecular mechanism of inhibiting the proliferation of human gastric cancer drug- resistant cells may be related to the upregulation of long non-coding RNAs and mRNAs contributed in CD95, mTOR, and TNF receptor signaling pathway.

Cite this article as: Abolhasani Zadeh F, Akbarirad M, Lian H, et al. Cellular and molecular mechanism of cell proliferation in human gastric cancer drug-resistant cells after hyperthermia and cisplatin: Role of mRNAs and long-non-coding RNAs. Turk J Gastroenterol. 2022;33(5):377-386.

EISSN 2148-5607