Reversing multidrug resistance of lung adenocarcinoma xenografts to gemcitabine in combination with cisplatin in mice by Kiwi essence and its mechanism / 肿瘤

ABSTRACT

Objective: To investigate the effect of Kiwi essence on sensitivity of lung adenocarcinoma xenografts in mice to gemcitabine in combination with cisplatin (DDP) (GP regimen) in mice, and to explore the possible mechanism. Methods: Forty C57BL/6J mice bearing tumor xenografts of Lewis cells were randomized into 5 groups control group (not tearted with Kiwi essence), high-dose (180 mg/kg) Kiwi essence group, GP group [DDP (3 mg/kg) + gemcitabine (50 mg/kg)], low-dose (60 mg/kg) Kiwi essence combined with GP group, and high-dose (180 mg/kg) Kiwi essence combined with GP group. The growth of tumor xenografts was observed. The mice were sacrificed 20 d after transplantation. The protein and mRNA expression levels of P-glycoprotein (P-gp) and glucose-regulated protein 78 (GRP78) in tumor xenografts were detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Results: The tumor growth was inhibited in various degrees in each drug intervention group as compared with that of the control group, and this inhibition effect was most significant in highdose (180mg/kg) Kiwi essence combined with GP group. The mRNA and protein expression levels of P-gp and GRP78 were significantly decreased in low-dose Kiwi essence combined with GP group, high-dose Kiwi essence group, and high-dose Kiwi essence combined with GP group, as compared with those of the control group and GP group (P < 0.01). The expression levels of P-gp and GRP78 proteins and mRNAs were significantly decreased in high-dose Kiwi essence group and high-dose Kiwi essence combined with GP group as compared with that of the low-dose Kiwi essence combined with GP group. Conclusion: Kiwi essence can obviously reverse the multidrug resistance of lung adenocarcinoma to GP chemotherapy in mice. This mechanism may be associated to the down-regulation of P-gp and GRP78.