| Background: Cisplatin is one of the primary chemotherapy drugs for treating tumors at present,whose advantages involving strong effect and wide spectrum of antitumor. Due to the lack of accurate recognition of tumor cells, cisplatin also exhibits serious cytotoxicity to normal cells as well as to tumor cells, causing extremely large side effects and reducing the expected therapy effects on tumor. In the prevention and treatment of tumors, it has become the key point that how to reduce the cytotoxicity of antitumor drugs and elevate the patient's tolerance to chemotherapy drugs. Curcumin, extracted from zingiberaceae plants, initially has been served as the natural colouring being applied to the food process industry. Some studies also demonstrate that curcumin has plenty of pharmacological effects, such as antioxidation, anti-inflammation, antitumor and so on. There have been established studies indicated that curcumin exerts antitumor effect when injected to the abdomen on the whole animal. But because of its insoluble property, oral way should be the most feasible approach of administration. It has not been reported that the oral way after digestion and absorption of gastric intestinal tract has the same antitumor effect as the abdominal injection. There also has not been reported the joint effect of curcumin by oral way with cisplatin.Objective: This study will take the leader to prove that curcumin gavage can coordinate with cisplatin to inhibit the growth of transplantation tumor in nude mice, and explore the related mechanisms, thus providing the theoretical basis for the clinical application of curcumin in anti tumor.Methods: The models of transplanted tumor from PC3 cells in nude mice were made and randomly divided into four groups(n=8): the vehicle control group, curcumin group, cisplatin group and cisplatin+curcumin group. The curcumin(200m/kg) was given 1 time a day by gavage for 20 days. The cisplatin(2mg/kg) was intraperitoneal injected 1 time a day,after the successive 5 days to stop for the following 10 days, then the same injection was given every day for another consecutive 5 days. As for the combined group, curcumin and cisplatin were individually given just as above-mentioned respective way. During the entire process, the volume of tumors were measured and calculated for every 5 days. The tumor growth curve was drawed. After 20 days of therapy, the nude mice were killed and the total RNA was extracted from the transplanted tumor tissues, then the expression changes of the proliferating cell nuclear antigen(PCNA) and the matrix metalloproteinase2(MMP2) were detected by real time RT-PCR method,and the protein expression was detected by immunohistochemistry.Results: There was significant difference of tumor volume in cisplatin group, cisplatin+curcumin group compared with control group after 15 days(p<0.01). On 20 th day, tumor volume of cisplatin+curcumin group was obviously smaller than that of curcumin group or cisplatin group. The amount of PCNA m RNA expression in all therapeutic groups were obviously lower than that of the control group(p < 0.01). Meanwhile, the amount of PCNA m RNA expression in cisplatin+curcumin group was obviously lower than that of cisplatin group or curcumin group(p<0.01). The changes of MMP2 m RNA expression in tumor tissues were similar to that of PCNA m RNA. The amount of MMP2 m RNA expression in combined cisplatin+curcumin group was obviously lower than that of cisplatin group or curcumin group(p<0.01). Similar changes of PCNA and MMP2 protein were observed in tumor tissues of each group.Conclusion:1. Curcumin by gavage can inhibit the tumor growth in PC3 transplanted nude mice2. Curcumin gavage combined with cisplatin can inhibit the tumor growth more effectively than the utility of cisplatin alone.3. The inhibitive effect on tumors of curcumin combined with cisplatin is associated with the gene inhibition of PCNA and MMP2. |
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