Screening of the Appropriate Proportion on Anti-Breast Cancer Activity of Prunellae spica Combined with Taraxaci herba and Its Anti-Tumor Research in Vivo
YAN Qing-zi, ZHANG Kai-qiang, LI Qiang, XIA Bo-hou, FU Rong-geng, WU Ping, LIN Yan, LIN Li-mei*, LIAO Duan-fang*
School of Pharmacy, Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan Engineering Laboratory for Prevention and Control Technology of Toxic Substances in Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China
Abstract��OBJECTIVE To screen optimal ratio of Prunella vulgaris(PV) and Taraxacum mongolicum(TM) as a synergetic combination for anti-breast cancer treatment in vitro based on combination index(CI) and to investigate the effects of PV and TM on cell proliferation and apoptosis under the optimized ratio in tumor-bearing(4T1) female BALB/c mice in vivo. METHODS Cell proliferation was assayed by MTT method. The dose-effect of PV combined with TM was evaluated by CI method, The combination has a synergistic effect when the CI value is less than 1. Breast cancer model was established by subcutaneous injection of 4T1 cells in BABL/c mice, the mice were given medicated feed daily for 25 d. Body weight and tumor growth were measured every three days. Histological change and cell apoptosis in tumor tissue from breast cancer mice were evaluated via HE and TUNEL methods. RESULTS The results indicated that cell proliferation of MCF-7 and MDA-MB-231 treated with PV and TM in combination was markedly inhibited. The combination index of PV and TM was 0.199 8 and 0.407 at a ratio of 4��3, which showed a synergistic effect. In addition, PV+TM treatment significantly reduced tumor volume without affecting body weight in breast cancer mice. HE staining showed that the infiltration of inflammatory cells appeared around the tumors and the areas of necrosis. TUNEL staining showed the induced apoptosis in tumor cells from breast cancer mice. CONCLUSION PV+TM combination has a significant anti-breast cancer activity possibly by boosting immunity and promoting apoptosis in tumor cells, which suggests that PV+TM combination might be a novel potent therapy for the treatment of breast cancer.
������,�ſ�ǿ,��ǿ,�IJ���,������,��Ƽ,����,������,�ζ˷�. �Ŀݲ������ѹ�Ӣ�����ٰ�����������ɸѡ�����ڿ������о�[J]. �й�ҩѧ��־, 2018, 53(10): 776-782.
YAN Qing-zi, ZHANG Kai-qiang, LI Qiang, XIA Bo-hou, FU Rong-geng, WU Ping, LIN Yan, LIN Li-mei, LIAO Duan-fang. Screening of the Appropriate Proportion on Anti-Breast Cancer Activity of Prunellae spica Combined with Taraxaci herba and Its Anti-Tumor Research in Vivo. Chinese Pharmaceutical Journal, 2018, 53(10): 776-782.
HAO J, DING X L, YANG X, et al. Prunella vulgaris polysaccharide inhibits growth and migration of breast carcinoma-associated fibroblasts by suppressing expression of basic fibroblast growth factor. Chin J Integr Med(�й����ҽѧ��־), 2016, 22(1):1-7.
[2]
LIN W, ZHENG L, ZHUANG Q, et al. Spica prunellae promotes cancer cell apoptosis, inhibits cell proliferation and tumor angiogenesis in a mouse model of colorectal cancer via suppression of stat3 pathway. BMC Complement Altern Med, 2013,13:144. doi: 10.1186/1472-6882-13-144.
[3]
OVADJE P, CHATTERJEE S, GRIFFIN C, et al. Selective induction of apoptosis through activation of caspase-8 in human leukemia cells(Jurkat) by dandelion root extract. J Ethnopharmacol, 2011, 133(1):86-91.
[4]
CHOU T C. Derivation and properties of Michaelis-Menten type and Hill type equations for reference ligands. J Theor Biol, 1976, 59(2):253-276.
[5]
CHOU T C. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev, 2006, 58(3):621-681.
[6]
YE T, XIONG Y, YAN Y, et al. The anthelmintic drug niclosamide induces apoptosis, impairs metastasis and reduces immunosuppressive cells in breast cancer model. PLoS One, 2014, 9(1):e85887.
[7]
PENG Q, CAI H, SUN X, et al. Alocasia cucullata exhibits strong antitumor effect in vivo by activating antitumor immunity. PLoS One, 2013, 8(9):e75328.
[8]
CHAN E, TAN M, XIN J, et al. Interactions between traditional Chinese medicines and Western therapeutics. Curr Opin Drug Discov Dev, 2010, 13(1):50-65.
[9]
ADAMS J M, CORY S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene, 2007, 26(9):1324-1333.
[10]
HOFFMAN R M. Orthotopic metastatic mouse models for anticancer drug discovery and evaluation: a bridge to the clinic. Invest New Drugs,1999,17(4):343-359.
[11]
LIAO D, LUO Y, MARKOWITZ D, et al. Cancer associated fibroblasts promote tumer growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One, 2009, 4(11):e7965.
[12]
WEBSTER N R, GALLEY H F. Inflammation and immunity. Bja Cepd Rev, 2011, 19(2):S2-S2.
[13]
GARDNER T E, NAAMA H, DALY J M. Peritoneal and splenic macrophage functions in the tumor-bearing host. J Surg Res, 1995, 59(2):305-310.
2018, Vol. 53 
