LncRNA and mRNA expression profiling reveals the molecular mechanism of hyperthermia sensitizing human gastric cancer cisplatin- resistant cell line SGC-7901/DDP

Gastric cancer (GC) is the second leading cause of cancer-related death in the world, but due to the emergence of drug resistance, the chemotherapy effect of GC has not been improved. Hyperthermia (HT) can increase the sensitivity of tumor cells to chemotherapeutic drugs and cause the specific expression of related genes. Therefore, we want to confirm that HT can enhance the sensitivity of SGC-7901/DDP cells to cisplatin (DDP) and explore the molecular mechanism of sensitization. To study the optimal experimental conditions with synergistic effect, temperature gradients (41 ℃, 44 ℃, 47 ℃, 50 ℃), time gradients (12 h, 24 h, 36 h) and DDP concentration gradients (1 μg/ml, 2 μg/ml, 3 μg/ml) were established. Then the microarray analysis was performed to explore the molecular mechanism of HT sensitization. Our results showed that 47 ℃ HT+ 2 μg/ml DDP for 24 h could synergistically inhibit the proliferation of SGC7901/DDP cells and significantly promote early apoptosis. Differentially expressed lncRNAs and mRNAs between groups were obtained. ENST00000434470.1(IDI2-AS1), ENST00000592689.1(TTN-AS1) and ENST00000412526.1(LINC00161) may play a pro-apoptotic role, while asRNAs could be a potential target for the treatment of GC. KEGG pathway enrichment showed that DDP+HT may induce apoptosis of SGC7901/DDP cells through GPCR signaling pathway, BARD signaling pathway and TRAIL signaling pathway. In summary, HT can enhance the sensitivity of SGC-7901/DDP cells to DDP by activating related apoptotic genes and pathways. The gene expression in SGC-7901/DDP cells was measured after treatment with 2 μg/ml cisplatin, 47 ℃ hyperthermia for 24 h, and 2 μg/ml cisplatin+47 ℃ hyperthermia for 24 h.