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<p>Oral cancer is a major health burden, with many patients presenting with late-stage disease and distant metastasis, contributing to higher morbidity and mortality. Surgery, chemotherapy, and radiotherapy are common treatment modalities for oral cancer. Chemotherapeutic drugs are effective in treating cancers; however, they also have various side effects that can affect patient survival rates. Docetaxel (DTX) and methotrexate (MTX) are used to treat multiple solid tumors. However, there are limited reports available on the efficacy of these drugs against oral cancer. Thus, in the present study, we investigated the effect of DTX and MTX as monotherapies on KB oral cancer cell lines. Initially, functional enrichment, gene ontology, and protein-protein interaction (PPI) analyses were performed to understand the key biological processes and interaction networks associated with DTX- and MTX-targeted genes in oral carcinoma. I<i>n vitro</i> analyses were conducted in KB cells treated with different concentrations of DTX (1.5–50 nM) and MTX (25 to 250µM) to identify the effective IC50 concentrations using MTT assay. Next, RT-PCR analysis was performed to evaluate the expression of 29 major genes involved in oral cancer, and apoptotic protein levels were analyzed using western blotting. DTX and MTX treatment resulted in significant upregulation of apoptotic and tumor suppressor genes, together with downregulation of oncogenes, drug transporters, growth factors, cell cycle regulators, and signal transduction genes. Western blot data showed that there was an increase in caspases (3,7, and 9) during DTX and MTX treatment in oral cancer cells. Moreover, enhanced DNA fragmentation, reduced cell migration, and decreased colony-forming ability have been observed. Overall, our data suggest that DTX showed a significant cytotoxic effect against oral cancer cells compared to MTX and could be used as an effective chemotherapeutic drug against oral cancer in the near future; however, extensive molecular investigations are still warranted.</p>

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In-silico and In-vitro Gene Expression Analysis on Docetaxel and Methotrexate-induced Cytotoxicity in Oral Cancer Cell Line

  • 期刊论文

  • 发表日期：

    2025年9月26日

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  • Maheshvare Natesan,
  • Rubin Nishanth Armstrong,
  • Krithika Narayanan,
  • Brindha G.R,
  • Devipriya Nagarajan,
  • Arpit Sikri,
  • Rekha Arcot,
  • Muthu Thiruvengadam,
  • Naiyf S Alharbi

摘要

Oral cancer is a major health burden, with many patients presenting with late-stage disease and distant metastasis, contributing to higher morbidity and mortality. Surgery, chemotherapy, and radiotherapy are common treatment modalities for oral cancer. Chemotherapeutic drugs are effective in treating cancers; however, they also have various side effects that can affect patient survival rates. Docetaxel (DTX) and methotrexate (MTX) are used to treat multiple solid tumors. However, there are limited reports available on the efficacy of these drugs against oral cancer. Thus, in the present study, we investigated the effect of DTX and MTX as monotherapies on KB oral cancer cell lines. Initially, functional enrichment, gene ontology, and protein-protein interaction (PPI) analyses were performed to understand the key biological processes and interaction networks associated with DTX- and MTX-targeted genes in oral carcinoma. In vitro analyses were conducted in KB cells treated with different concentrations of DTX (1.5–50 nM) and MTX (25 to 250µM) to identify the effective IC50 concentrations using MTT assay. Next, RT-PCR analysis was performed to evaluate the expression of 29 major genes involved in oral cancer, and apoptotic protein levels were analyzed using western blotting. DTX and MTX treatment resulted in significant upregulation of apoptotic and tumor suppressor genes, together with downregulation of oncogenes, drug transporters, growth factors, cell cycle regulators, and signal transduction genes. Western blot data showed that there was an increase in caspases (3,7, and 9) during DTX and MTX treatment in oral cancer cells. Moreover, enhanced DNA fragmentation, reduced cell migration, and decreased colony-forming ability have been observed. Overall, our data suggest that DTX showed a significant cytotoxic effect against oral cancer cells compared to MTX and could be used as an effective chemotherapeutic drug against oral cancer in the near future; however, extensive molecular investigations are still warranted.