Abstract
The development of chemoresistance in patients represents a major challenge in cancer treatment. Lactate dehydrogenase-A (LDHA) is one of the principle isoforms of LDH that is expressed in breast tissue, controlling the conversion of pyruvate to lactate and also playing a significant role in the metabolism of glucose. The aim of this study was to identify whether LDHA was involved in oral cancer cell resistance to Taxol and whether the downregulation of LDHA, as a result of cisplatin treatment, may overcome Taxol resistance in human oral squamous cells. The OECM-1 oral epidermal carcinoma cell line was used, which has been widely used as a model of oral cancer in previous studies. The role of LDHA in Taxol and cisplatin resistance were investigated and the synergistic cytotoxicity of cisplatin and/or Taxol in oral squamous cells was analyzed. Cell viability was analyzed by MTT assay, LDHA expression was analyzed by western blot analysis and siRNA tranfection was performed to knock down LDHA expression. The present study results showed that decreased levels of LDHA were responsible for the resistance of oral cancer cells to cisplatin (CDDP). CDDP treatments downregulated LDHA expression, and lower levels of LDHA were detected in the CDDP-resistant oral cancer cells compared with the CDDP-sensitive cells. By contrast, the Taxol-resistant cancer cells showed elevated LDHA expression levels. In addition, small interfering RNA-knockdown of LDHA sensitized the cells to Taxol, but desensitized them to CDDP treatment, while exogenous expression of LDHA sensitized the cells to CDDP, but desensitized them to Taxol. The present study also revealed the synergistic cytotoxicity of CDDP and Taxol for killing oral cancer cells through the inhibition of LDHA. This study highlights LDHA as a novel therapeutic target for overcoming Taxol resistance in oral cancer patients using the combined treatments of Taxol and CDDP.
Highlights
Taxol is a valuable cancer chemotherapeutic agent used for the treatment of numerous types of cancer, including ovary, breast, oral and lung carcinomas [1,2,3,4]
The present study investigated which signaling pathway may be involved in CDDP resistance, according to Lactate dehydrogenase‐A (LDHA) expression
Following screening, which involved the investigation of mitochondrial oxidation consumption, the AKT and mTOR pathway and microRNAs which may target glycolysis and mitochondrial apoptosis pathways, including cytochrome c and Bcl-2, the expression of LDHA was found to be significantly decreased subsequent to CDDP treatment at varying doses in two oral cancer cell lines (P
Summary
Taxol (paclitaxel) is a valuable cancer chemotherapeutic agent used for the treatment of numerous types of cancer, including ovary, breast, oral and lung carcinomas [1,2,3,4]. The primary cellular targets of Taxol are the microtubules of cancer cells, which are vital for mitotic activity, cellular motility and proliferative capacity [3]. Taxol is known to block cell replication, arrest cells in the G2/M phase of the cell cycle and induce apoptosis [5,6]. Mechanisms accounting for Taxol resistance include alterations to the tubulin structure [7,8,9], changes in the drug‐binding affinity of the microtubules [10] and cell cycle deregulation [11]. The detailed molecular mechanisms that may contribute to the Taxol resistance of cancer cells are not fully understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
