Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

Abstract

Background: Cephalosporin antibiotics can drastically upregulate the expression of HMOX1 in nasopharyngeal carcinoma cells. HMOX1 has dual role in cancer cells, and is involved in chemoresistance. Cephalosporin antibiotics are widely used in the treatment of bacteria infectious diseases in cancer patients. Whether they affect the efficacy of chemotherapy is unknown. Methods: Comparisons between cefotaxime and the combination of cefotaxime and cisplatin were carried out throughout the study. Cell viability was detected by MTT method. Influence on clone formation of cancer cells was investigated by plate clone formation assay. The in vivo anticancer effect was determined via cancer xenograft in mice. Flow cytometry analysis was used to detect the apoptosis. Microarray gene expression profiling was analyzed using Gene Ontology analysis, and the differential genes were validated by RT-qPCR. Results: Cefotaxime specifically, selectively and synergistically enhanced the anticancer efficacy of cisplatin in nasopharyngeal carcinoma both in vitro and in vivo without increasing the toxicity, but it inhibited the cytotoxic effects of cisplatin in other cancers. Combination of cefotaxime and cisplatin significantly regulated 5 genes in direction favoring the enhancement of anticancer efficacy; of which, THBS1 and LAPTM5 were upregulated; PPP3CB, STAG1 and NCOA5 were downregulated jointly. HMOX1 contributes to the anticancer efficacy in combination group. Upregulated genes significantly modulated 18 apoptotic pathways, downregulated genes mainly affected assembly of genetic materials. Conclusion: Cephalosporin antibiotics are excellent and safe sensitizers of conventional chemotherapy in the treatment of nasopharyngeal carcinoma, but should be carefully used in other cancers.