RESUMO
BACKGROUND: Colon cancer has high mortality rate which making it one of the leading causes of cancer deaths. Oxaliplatin is a common chemotherapeutic drug, but it has disadvantages such as drug resistance. OBJECTIVE: The purpose of this study is to explore the mechanism of exosomes in the resistance of oxaliplatin and verify whether elemene and STAT3 inhibitors reverse the resistance to oxaliplatin. METHODS: Related cell line models were constructed and the proliferation, migration, invasion, apoptosis and resistance to oxaliplatin were evaluated for all three cells of HCT116/L, sensitive cell HCT116 and HCT116+HCT116/L-exosomes (HCT116-exo). It was to explore probable signaling pathways and mechanisms by Western blotting. RESULTS: HCT116-exo drug-resistant chimeric cells showed greater capacity for proliferation, migration and invasion than HCT116 sensitive cells. After the above cells were treated with oxaliplatin, the apoptosis rate of chimeric drug-resistant cells HCT116-exo and its IC50 increased compared with the sensitive cells HCT116. The proliferation, invasion and migration of cells treated with STAT3 inhibitor or ß-elemene combined with oxaliplatin reduced compared with those treated with oxaliplatin or ß-elemene alone. The STAT3 inhibitor or ß-elemene in combination with oxaliplatin increased the rate of apoptosis relative to oxaliplatin or ß-elemene alone. Drug-resistant cell exosomes could promote the EMT process, related to the participation of FGFR4, SHMT2 and STAT3 inhibitors. CONCLUSION: Drug-resistant cell exosomes could induce resistance, and improve the capacity of colon cancer towards proliferate, invade, migrate and promote the EMT process. The ß-elemene combined with oxaliplatin could reverse the above results which might be related to the STAT3 pathway and EMT pathway in colon cancer.
RESUMO
Background: Gastric cancer (GC) is one of the most common malignant tumours in the digestive system. Serine hydroxymethyltransferase 2 (SHMT2) is one of the key enzymes associated with serine metabolism. However, the prognostic role of SHMT2 in GC carcinogenesis has yet to be studied. Methods: The expression of SHMT2 in human tumors and normal tissues was detected by the Assistant for Clinical Bioinformatics and Immunohistochemistry (IHC). The relationship of the expression of SHMT2 with clinical characteristics and survival data was analysed by the chi-square test, survival analysis and online databases. Finally, the correlation between SHMT2 expression and associated signalling channels, and molecules was analysed by online databases. Results: SHMT2 was strongly expressed in numerous human cancers. The expression rate of SHMT2 was 56.44% in GC (P = 0.018). The survival analysis indicated that patients with high expression of SHMT2 had the worse overall survival (OS; log-rank P = 0.007). The expression of SHMT2 was correlated with tumour size (P = 0.034) and, TNM stage (P = 0.042). In particular, SHMT2, vessel invasion and M stage were independent factors for OS in GC (P = 0.044, P < 0.001, P < 0.001). The SHMT2 gene was substantially correlated with cell signalling pathways. Conclusions: SHMT2 is highly expressed in GC and is associated with a poor prognosis. The exploration of its mechanism may be related to tumour proliferation, DNA repair and replication. SHMT2 is an independent prognostic risk factor and a potential biomarker for the diagnosis and treatment of GC.