Anticancer Effect And Mechanism Of Plumbagin On Lewis Lung Carcinoma In Vitro And In Vivo

Objective:To study the the inhibitive effect of plumbagin on Lewis lung cancer.Methods:1.Cell apoptosis of plumbagin against lewis lung carcinoma cells was studied by CCK-8 assay. 2. Apoptosis was determined by flow cytometry. 3. The expression of VEGF mRNA was detected by qRT-PCR. 4. The expression of Bcl-2 and VEGF protein was studied by Western blot assay. 5. The model of C57BL/6 mice bearing Lewis lung cancer was established by subcutaneous seeding of Lewis lung cancer cells, and randomly divided into 5 groups(n=6); Tumor-bearing mice were injected with normal saline, plumbagin(low,medium or high dose) or cyclophosphamide(CTX)in each group; The tumor volume was measured; All mice were sacrificed on Day22 nd under aseptic condition for the tumor collection; The transplanted tumors were weighed for calculation of the tumor inhibition rate; Immunohistochemical method was applied to assessing the VEGF expression in tumor tissue.Results:1. CCK-8 assay showed that plumbagin had an obvious inhibition on lewis lung carcinoma cells line in a dose-dependent manner(P<0.05). 2. After treated with plumbagin for 24 h, the apoptosis rate was(4.84±0.54)%,(10.37±1.15)%,(20.27±2.51)% at 2.5?mol/L,5.0?mol/L and 10?mol/L of plumbagin, respectively,when compared to(2.45±1.09)% in untreated cells(P<0.05). 3.The expression of VEGF mRNA was suppressed,as compared with the control group(p<0.05). 4. The protein levels of Bcl-2 and VEGF were significantly reduced by plumbagin(0?2.5?5?10?mol/L) treatment(P<0.05). 5. In plumbagin(low,medium or high dose) groups and CTX group, tumor volume were significantly smaller than that in control group on Day 10 th,13th,16 th and 19th(P<0.05).Tumor volume between in plumbagin(low,medium or high dose) groups(p<0.05). The inhibitory rates on mouse tumor of low dose plumbagin group?medium dose plumbagin group?high dose plumbagingroup and CTX group are 14.48%?31.47%?48.27%?57.76%. The tumor weight on plumbagin(low,medium or high dose) groups and CTX group were significantly smaller than control group(F=33.253,P=0.000).VEGF expression between in plumbagin groups or CTX group and control group(F=153.52,P=0.000).Conclusion:1. Plumbagin can induce cell apoptosis, down-regulate the expression of Bcl-2,VEGF and inhibit the proliferation of lewis lung carcinoma cells. 2.Plumbagin suppressed tumor growth of LLC in mice, down-regulates the expression of VEGF.