Cisplatin therapy for in vivo enrichment of gastric cancer stem cells / 中国组织工程研究

ABSTRACT

BACKGROUND:Tumor stem cels have self-renewal, drug resistance and metastasis tumorigenicity, which play an important role in occurrence, development and metastasis of tumors. Currently, there are two methods to identify tumor stem cels, namely, in vitro tumor sphere culture experiments and in vivo mouse tumorigenic experiments. However, there ia a lack of reports regarding clinicaly enriched gastric cancer cels by chemotherapy. OBJECTIVE:To investigate the enrichment of rat gastric cancer stem cels by cisplatin, and to explore the screening methods for their surface marker proteins. METHODS: BCG-823 gastric cancer model was established in rats, and then rat models were randomized into two groups rats in experimental groups were subjected to intravenous injection of 0.1, 0.2, 0.25, 0.3 g/L cisplatin via the tail vein; those in control group were injected with normal salinevia the tail vein. After three courses of chemotherapy, gastric stem cels-enriched tissues were colected. Tumor surface proteins were extracted using high-throughput protein microarray and identified by western blot assay. Effects of cisplatin on enrichment of rat gastric cancer stem cels and screening methods for surface marker proteins were compared. RESULTS AND CONCLUSION:Cisplatin at a dose of 0.3 g/L×200μL exhibited the best therapeutic effects, and moreover, with the dose increasing, the tolerance became worse and the incidence of adverse reaction became higher. Transplantation tumors were verified by hematoxylin-eosin staining. Western blot test results were similar to the findings of protein microarray method, that is, HLA-DQ, PMP22 and Claudin7 protein expressions increased in gastric tissues, but HLA-DR, CD14, CD16 and CD56 protein expression decreased. These findings suggest that cisplatin can be used to enrich gastric cancer stem cels in rats, and to successfuly screen the corresponding surface marker proteins.