Experimental Study On Inhibitory Effect Of Panax Notoginseng Saponins On Subcutaneous Xenografts Of Cholangiocarcinoma In Mice

[Objective]:We study the tumor inhibition effect of Notoginsenoside treatment on Cholangiocarcinoma mouse model in vivo. This intervention could have a great potential in treating Cholangiocarcinoma.[Methods]:We created the Cholangiocarcinoma mouse model by injecting0.2ml (1.0x107/ml) Mouse Cholangiocarcinoma (MC) cells into the subcutaneous tissue of the mouse’s right axillary fossa. After inoculating the tumor cells for6days,33tumor bearing mice were successfully established, with an average tumor size of6mm×5mm×5mm. We selected30mice and divided them equally into3different treatment groups which we performed abdominal injection treatments on each group every other day for7times. These three treatment groups include:NS control group (injected with0.2ml0.9%NS),5-FU group (injected with0.2ml5-FU) and Notoginsenoside group (injected with0.2ml Notoginsenoside). The changes in tumor size were measured during each injection. At day20, all the mice were sacrificed and tumors were removed for further testing. Five randomly selected mice from each group were tested for white blood cell counts and lymphocyte counts. We also measured the final tumor weight and size. Biopsy analyses were performed on tumor, liver and spleen tissues using HE staining. Finally, flow cytometry was used to detect the cell cycle stage of these tumor tissues.[Results]:We successfully developed the Cholangiocarcinoma mouse model for this study. The tumor size and weight under Notoginsenoside treatment were significantly reduced (p<0.05), when compared to the control group. The WBC and lymphocyte counts stay normal in Notoginsenoside group while significantly reduced (P<0.05) in5-FU group as compared to the control group. Finally, flow cytometry showed that5-FU increases Go/G1cell cycle phase, but decreases both S and G2/M phases, which suggest possible inhibition of DNA synthesis. On the other hand, Notoginsenoside decreases both G0/G1and S phases, but increases G2/M cell cycle phase, which indicate repression of cell mitosis.[Conclusion]:Our study showed that Notoginsenoside treatments can reduce the tumor size and weight and eventually inhibit tumor growth. We also observed that Notoginsenoside had no toxic effect on white blood cells and lymphocytes counts in these mice; Pathologic results indicated there were no metastasises in both liver and spleen; Notoginsenoside can also inhibit the tumor cells proliferation by blocking its transition from G2phase to M phase. Therefore, we have presented some evidences that Notoginsenoside could be potential treating for Cholangiocarcinoma.