Betulinic acid induces apoptosis and impairs migration and invasion in a mouse model of ovarian cancer
Betulinic acid induces apoptosis and impairs migration and invasion in a mouse model of ovarian cancer
复制标题
DOI：
10.1111/jfbc.13278
复制
发表时间：
2020-05-15
影响因子：
4
通讯作者：
Zhou Jieli
中科院分区：
文献类型：
--
作者：
Liao Lingyun;Liu Chi;Zhou Jieli
白桦酸（BA）具有抗肿瘤、抗炎等多种生物活性。在我们的研究中，我们研究了BA对卵巢癌细胞的生长抑制、促进细胞凋亡和抵抗转移的作用。结果表明，BA对卵巢癌细胞系的抑制作用具有时间和剂量依赖性。SKOV3细胞系的增殖具有浓度依赖性和时间依赖性，BA可能抑制SKOV3细胞系的增殖。此外，BA通过抑制上皮-间质转化过程显著抑制肿瘤细胞的转移。此外，BA能明显抑制SKOV3细胞荷瘤小鼠皮下肿瘤的重量和体积。病理和免疫组化检测显示，BA给药后Ki-67（+）和MMP-2（+）细胞显著减少，说明BA不仅能抑制肿瘤细胞的增殖，还能抑制肿瘤细胞的迁移。综上所述，BA可能是治疗卵巢癌的一种有价值的候选药物。白桦酸（baulinic acid， BA）从葫芦巴、桉树球茎和桑树等天然植物中分离得到，具有多种生物活性。本研究结果表明，ba在体外和体内均能诱导人卵巢癌细胞凋亡，抑制卵巢癌细胞的迁移和侵袭。因此，天然植物BA有可能成为抑制卵巢癌细胞发育的潜在药物。
Betulinic acid (BA) was verified to possess plenty of biological activities including anti-tumor, anti-inflammatory and so on. In our research, we studied the growth inhibition, apoptosis promotion and metastasis resistance of ovarian cancer cells by BA. The result showed that BA showed a time- and dose-dependent inhibitory effect on ovarian cancer cell lines. SKOV3 cell line proliferation has a concentration- and time-dependently, which may be inhibited by BA. Furthermore, BA inhibited the metastasis of tumor cells remarkably by inhibiting epithelial-mesenchymal transition process. Beyond that, the weight and volume of subcutaneous tumor was distinctly suppressed by administration of BA in tumor-bearing mice of SKOV3 cells. Pathological and immunohistochemical tests showed that Ki-67(+) and MMP-2(+) cells were dramatically decreased after BA administration, indicating that BA can not only suppress proliferation, but also inhibit migration of tumor cells. Taken together, BA can be a valuable candidate drug for the treatment of ovarian cancer.Practical applications Betulinic acid (BA) isolated from natural plants such as fenugreek, eucalyptus bulb and mulberry has been reported with many biological activities. Results from this study revealed that in vitro and in vivo BA-induced apoptosis and inhibited migration and invasion of human ovarian cancer cells. Therefore, BA from natural plants may be developed as a potential drug for inhibition the development of ovarian cancer cells.