<p>5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs. In this study, we aimed to investigate the impact of PYGO2 overexpression on the sensitivity of YM-1 and KYSE-30 esophageal carcinoma&#xa0;cells against 5-FU. To do this, we compared cell viability, cell cycle arrest, apoptosis rate, and mRNA expressions of various apoptosis-related genes between pcDNA3-PYGO2 transfected and untransfected KYSE-30 and YM-1 esophageal carcinoma cells following treatment with 5-FU. We showed that PYGO2 expression reduces 5-FU sensitivity in YM-1 and KYSE-30 cells. PYGO2-overexpressing cells treated with 5-FU have exhibited a noteworthy reduction in both early and late apoptotic cells compared to controls. Furthermore, a significant decrease in the Bax/Bcl2 ratio and P53 gene expression was observed. 5-FU induces G2/M cell cycle arrest in YM-1 and KYSE-30 cells. However, PYGO2 overexpression impeded G2/M cell cycle arrest in 5-FU-treated cells, thereby suppressing the toxicity of 5-FU. PYGO2 may mediate its apoptotic effect by regulating cell cycle regulatory proteins, specifically cyclin D1 and p21. These results highlight PYGO2’s capacity to alter how esophageal cancer cells respond to 5-FU therapy, emphasizing its importance as a potential focal point for treatment strategies.</p>

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PYGO2 promotes resistance to chemotherapy via reducing apoptosis and G2/M cell cycle arrest in esophageal carcinoma cells

  • Fatemeh Ardalan Moghadam Al,
  • Mohammad Mahdi Forghanifard,
  • Vajiheh Zarrinpour

摘要

5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs. In this study, we aimed to investigate the impact of PYGO2 overexpression on the sensitivity of YM-1 and KYSE-30 esophageal carcinoma cells against 5-FU. To do this, we compared cell viability, cell cycle arrest, apoptosis rate, and mRNA expressions of various apoptosis-related genes between pcDNA3-PYGO2 transfected and untransfected KYSE-30 and YM-1 esophageal carcinoma cells following treatment with 5-FU. We showed that PYGO2 expression reduces 5-FU sensitivity in YM-1 and KYSE-30 cells. PYGO2-overexpressing cells treated with 5-FU have exhibited a noteworthy reduction in both early and late apoptotic cells compared to controls. Furthermore, a significant decrease in the Bax/Bcl2 ratio and P53 gene expression was observed. 5-FU induces G2/M cell cycle arrest in YM-1 and KYSE-30 cells. However, PYGO2 overexpression impeded G2/M cell cycle arrest in 5-FU-treated cells, thereby suppressing the toxicity of 5-FU. PYGO2 may mediate its apoptotic effect by regulating cell cycle regulatory proteins, specifically cyclin D1 and p21. These results highlight PYGO2’s capacity to alter how esophageal cancer cells respond to 5-FU therapy, emphasizing its importance as a potential focal point for treatment strategies.