PNS-Rb1 Reverse Effect On Tumor Multidrug Resistance In Vivo Study

Objectives:Multidrug resistance (multidrug resistance, MDR) is the result of the important reasons for failure of cancer chemotherapy, drug resistance reversal agents find the right cancer drug research has become a key issue. PNS-Rbl is the main active ingredient of Chinese medicine Panax, PNS-Rb1 is the main active ingredient of Chinese medicine Panax, with more targets, high efficiency, low toxicity and reversing tumor drug resistance, and its potential clinical application and deserves further research and development. This experiment intended for the P-gp-mediated multidrug resistance phenomenon, the establishment of MFC/5-Fu drug-resistant cell sublines and resistant tumor models to investigate the in vivo experiments, PNS-Rb1 resistance reversal effect of its and the mechanism for the PNS-Rb1 as a resistance reversal agents to provide experimental basis for clinical application.Methods:Induced by concentration gradient was established by stable growth and passage to the MFC/5-Fu drug-resistant cell sublines, and further by subcutaneous inoculation of resistant tumor models to establish stable MFC/5-Fu randomly grouped with different concentrations of PNS-Rb1 or DDP and 5-FU combination therapy, compared weight changes in mice, tumor, liver weight and tumor metastasis, inhibitory rate was calculated, and by flow cytometry and immunohistochemistry to detect MDR1/P-gp, MRP1, Ki-67 and VEGF expression.Results:1. Gradually increasing drug concentrations used ultimately in 4.5μg/ml of 5-Fu in the culture medium containing drug stable growth MFC/5-Fu of drug-resistant cell sublines;2. Successfully established by subcutaneous inoculation of resistant tumor models stable MFC/5-Fu;3. FCM and immunohistochemistry showed that compared with the MFC, MFC/5-Fu resistance P-gp expression in tumors was significantly higher (P <0.01), while the expression of MRP1 was no significant difference between the groups (P> 0.05);4. PNS-Rb1 were randomly assigned treatment with MFC/5-Fu and MFC body weight of mice, tumor, liver weight and no significant difference in tumor inhibition rate (P> 0.05);5. Immunohistochemistry showed that the expression of VEGF and Ki67 in all treatment groups no significant difference (P> 0.05);6. PNS-Rb1 treatment by flow cytometry and immunohistochemistry showed no cytotoxic concentrations of PNS-Rb1 (50mg/kg, 100mg/kg) combined 5-Fu or DDP group and control group or a simple 5-Fu chemotherapy group compared, P-gp expression was significantly decreased (P<0.01), while the PNS-Rb1 combined 5-Fu or DDP group and the VRP combined 5-Fu or DDP group comparison, P-gp expression was significantly decreased (P<0.01), but the expression of MRP 1 in the treatment group difference among groups was not significant (P> 0.05)。Conclusions:1. MFC/5-Fu of drug-resistant cell sublines and resistant tumor models showed the typical model of multi-drug resistance phenotype, its main mechanism of resistance to intracellular P-gp over-expression;2. PNS-Rbl on MFC/5-Fu resistant tumor growth, invasion, metastasis and angiogenesis of no effect;3. High levels of PNS-Rb1 (100mg/kg) with a certain anti-tumor effect;4. No cytotoxic concentrations of PNS-Rb1 (50mg/kg, 100mg/kg) can be reduced MFC/5-Fu resistance P-gp expression in tumors, could partially reverse the MFC/5-Fu multidrug resistance of tumor drug resistance Herbs, PNS-Rb1 reversing tumor drug resistance was superior to verapamil;5. PNS-Rb1 is a safe and effective MDR reversal agents, with a more broad application prospects.