Experimental study of human bone marrow mesenchymal stem cells on regulating the biological characteristics of gastric cancer cells / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the regulatory mechanism of bone marrow mesenchymal stem cells(BMSC) on the biological profiles of KATO-III( cell lines of gastric cancer.</p><p><b>METHODS</b>Transwell cubicle was applied to build the co-cultured model in non-contact style. The differences of cell proliferation and the resistance of anti-tumour drug (5-fluoropyrimidinedione, 5-FU and Cisplatin, CDDP) between co-cultured group and single cultured group were evaluated by Cell Counting Kit 8-assay(CCK-8). The invasion ability was detected by Transwell assay. The expressions of stem cell makers, apoptosis-related factors and epithelium-mesenchymal transition (EMT)-related factors were detected by RT-PCR.</p><p><b>RESULTS</b>The proliferation ability of KATO-III( cells in co-cultured group was significantly stronger than that in single cultured group. The growth rate of KATO-III( cells in co-cultured group was significantly higher than that in single cultured group after treatment of 5-FU and CDDP(P<0.05). The mRNA expression level of Bcl-2 was significantly higher in co-cultured group KATO-III( cells(P<0.05), while the mRNA expression level of Bax was significantly lower in co-cultured group KATO-III( cells(P<0.05) in comparison with those in single cultured group. As compared to KATO-III( cells in single cultured group, the number of infiltrating-membrane cells was significantly higher (37.33±5.22 vs 14.56±2.54, P<0.01) in co-cultured group, and the mRNA expression levels of Snail and N-cadherin were significantly higher in co-cultured group KATO-III( cells (P<0.05), while the mRNA expression level of E-cadherin was significantly lower in co-cultured group KATO-III( cells (P<0.05). The expressions of CD133, Nanog and Sox-2 mRNA in co-cultured group KATO-III( cells were significantly higher than those in single cultured group(P<0.05).</p><p><b>CONCLUSIONS</b>In co-cultured model sharing non-contact style, BMSC can enhance such properties of KATO-III( gastric cancer cells as the proliferation, the invasion and the chemoresistance. Furthermore, the regulatory mechanisms may be related to the increase of the expressions of some stem cell markers in gastric cancer cells.</p>

Influence of CD133+expression on patients' survival and resistance of CD133+cells to anti-tumor reagents in gastric cancer

Objective: To investigate the influence of CD133+expression on patients' survival and resistance of CD133+cells to anti-tumor agents in gastric cancer (GC). Methods: Influence of CD133 expression on prognosis was analyzed employing sam-ples from patients with GC. GC cell lines were utilized to separate CD133+and CD133?subpopulations by immunomagnetic separation and to analyze the biological features of two subpopulations in vitro and in vivo, especially in resistant to anti-tumor reagents and its apoptotic mechanism. Results: The lower CD133+group showed a significantly better survival compared with the higher CD133+group. The highest content of CD133+subpopulations for KATO-III cells had stronger proliferative ability than CD133?subpopulations. A single CD133+cell was capable of generating new cell colony and the tumorigenicity rate in nude mice was 100% for CD133+ clonal spheres or for CD133+ cells, but 0% for CD133? cells. Furthermore, the higher expression levels of Oct-4, Sox-2, Musashi-1 and ABCG2 in CD133+ clonal spheres were identified compared with CD133+ cells or CD133? cells. Under the treatment of anti-tumor reagents, CD133+ cells had lower suppression rates compared with CD133? cells while lower level of Bcl-2 and higher level of Bax were found in CD133+cells compared with CD133?cells. Conclusions: The patients with lower CD133+expression had a better survival. Enriched CD133+ cells in clonal sphere shared the ability to be self-renewable, proliferative, tumorigenic and resistant to anti-tumor agents as probably regulated by Bcl-2 and Bax.