RESUMO
BACKGROUND:Tumor has been considered as a specific nonhealing trauma. Bone marrow mesenchymal stem cel s participate in tumor mesenchymal reconstitution by tumor tissue homing and differentiation into mesenchyme, resulting in changing tumor microenvironment and affecting tumor growth and transfer. OBJECTIVE:To explore the mechanisms of participation of bone marrow mesenchymal stem cel s in tumor tissue repair in an A549 lung cancer-bearing mouse model. METHODS:Bone marrow mesenchymal stem cel s were isolated in vitro, cultured, and identified using flow cytometry, and then used to establish a mouse model of A549 lung cancer-bearing. In the experimental group, human bone marrow mesenchymal stem cel s were injected into tissue surrounding the tumor. In the control group, an equal volume of PBS was injected. Animal survival condition and tumor size were compared. At 4 weeks, the specimens were harvested. Hematoxylin-eosin staining was used to compare tumor tissue. Masson staining was utilized to compare col agen fiber content. Reverse transcription-PCR was employed to detect the expression ofα-smooth muscle actin. Immunohistochemistry was used to examine the expression of fibroblast specific protein and fibroblast activation protein to reflect the degree of interstitial fibers in tumor tissue in both groups. The expression levels of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C were compared between the two groups using immunohistochemistry. RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cel s promoted tumor growth in tumor-bearing mice. The growth rate of tumor tissue in experimental group was faster than the control group (P<0.05). Compared with the control group,α-smooth muscle actin mRNA expression was significantly higher in the experimental group. Immunohistochemistry was used to detect the expression of tumor angiogenesis factors markers (fibroblast specific protein and fibroblast activation protein) in tumor tissue of experimental group. The expression levels of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C were significantly greater in the experimental group than in the control group (P<0.05). Results indicated that bone marrow mesenchymal stem cel s differentiated into fibroblasts in tumor microenvironment, participated in the formation and construction of tumor stroma as wel as promoted the growth and repair of tumor via the secretion of vascular endothelial growth factor, hepatocyte growth factor, interleukin-6 and tenescin-C.
RESUMO
Objective To investigate whether octreotide,as somatostatin analogue,can enhance the sensitivity of the human lung adenocarcinoma cell line A549 to chemotherapeutic drugs.Methods Different concentration of octretide,cisplatin and 5-Fluorouracil (5-Fu) was respectively acted on the lung adenocarcinoma cell line A549.The absorbance value was tested by colorimetry through MTT method to evaluate the effect of octreotide,cisplatin,5-Fu or the three drugs combined respectively after 48 hours.Each drug concentration had six holes and it repeated three times.The effects of combination therapy was analysed with isobologram.Results It was proved that octreotide could inhibit the proliferation of A549 cells in a dose-dependent manner at the concentration range of 1.3 mg/L ～ 166.7 mg/L.The inhibition rate was dose-dependent which was higher when octreotide combined with cisplatin and 5-Fu than it alone.It has statistically significant difference (P ＜ 0.05 ).The effect plots of IC50 were located in the synergy areas of isobologram.Conclusion It can be concluded that octreotide could inhibit the proliferation of A549 cells in vitro.This inhibition enhances when octreotide is combined with cisplatin and 5-Fu.Octreotide can enhance the susceptibility of A549 cells to cisplatin and 5-Fu.
