ABSTRACT
ObjectiveTo study the effect of Xihuangwan extract on mitochondrial energy metabolism in ovarian cancer SKOV3 and HEY cells and to explore the underlying mechanism. MethodSKOV3 and HEY cells were cultured in vitro and treated with different concentrations （0， 5， 10， 15， 20 g·L-1） of Xihuangwan extract. Methyl thiazolyl tetrazolium （MTT） was used to examine the viability of SKOV3 and HEY cells treated with Xihuangwan extract. The adenosine-triphosphate （ATP） levels in SKOV3 and HEY cells were measured by kit. Flow cytometry was employed to measure the content of reactive oxygen species （ROS） in cells. Western blot was employed to determine the protein levels of peroxisome proliferator-activated receptor-γ co-activator 1α （PGC1α）， transcription factor A， mitochondrial （TFAM）， translocase of outer mitochondrial membrane 20 （TOMM20）， and aplasia Ras homologue member Ⅰ （ARHⅠ） in SKOV3 and HEY cells. Mito-Tracker Green staining was used to observe the morphological changes of mitochondria in SKOV3 and HEY cells. ResultCompared with blank group， Xihuangwan extract treatment for 24， 48 h inhibited the viability of SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）. Compared with blank group， Xihuangwan extract （10， 15， 20 g·L-1） groups presented lowered ATP levels （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had lower ATP level than the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with blank group， Xihuangwan extract increased the content of ROS in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the 20 g·L-1 Xihuangwan extract group had higher ROS content than the 10 g·L-1 Xihuangwan extract group （P<0.05）. Compared with blank group， Xihuangwan extract up-regulated the expression level of ARHⅠ protein in SKOV3 and HEY cells in a concentration-dependent manner （P<0.01）， and the expression levels of ARHⅠ protein was higher in the 20 g·L-1 Xihuangwan extract group than in the 10 and 15 g·L-1 Xihuangwan extract groups （P<0.05）. Compared with the blank group， Xihuangwan extract down-regulated the protein levels of PGC1α， TFAM， and TOMM20 in SKOV3 and HEY cells in a concentration-dependent manner （P<0.05， P<0.01）， and the protein levels of TFAM and TOMM20 in the HEY cells treated with 20 g·L-1 Xihuangwan extract were lower than those in the HEY cells treated with 10， 15 g·L-1 Xihuangwan extract （P<0.05）. Compared with the blank group， 20 g·L-1 Xihuangwan extract decreased the Mito-Tracker fluorescence intensity of SKOV3 and HEY cells （P<0.05）. ConclusionXihuangwan can compromise the mitochondrial function of ovarian cancer SKOV3 and HEY cells and reduce cell energy metabolism to inhibit the proliferation of SKOV3 and HEY cells by up-regulating ARHⅠ and inhibiting PGC1α/TFAM signaling axis.
ABSTRACT
ObjectiveOvarian cancer is the third most common gynecologic cancer worldwide， with the second highest mortality rate among gynecologic cancers， and age-standardized rates are gradually increasing in many low- and middle-income countries. At present， its etiology and pathogenesis are not clear. There are no obvious symptoms in the early stage， and when the symptoms become obvious， it often indicates the advanced stage. The 5-year survival rate of the advanced stage is only 17%， which poses a great threat to women's health. Therefore， an in-depth study of the etiology and pathogenesis of ovarian cancer is very important to the exploration of prevention and treatment methods for ovarian cancer. Based on the clinical characteristics of ovarian cancer in traditional Chinese and Western medicine， and combined with the existing evaluation methods of animal models， this study evaluated the animal model of ovarian cancer， and provided analysis and suggestions. MethodThis study searched China National Knowledge Infrastructure （CNKI）， Wanfang data， VIP information database， and PubMed database using the keywords "ovarian cancer" and "animal model"， excluded the articles that did not meet the criteria， and then classified the remaining studies. Combined with the clinical diagnostic criteria of Western medicine and traditional Chinese medicine syndrome differentiation， the related indicators of ovarian cancer animal models were assigned and the degree of agreement was evaluated. ResultThe use of the transplanted animal model exhibited the highest frequency， followed by that of the induced model. The degree of agreement of traditional Chinese medicine for each model was lower than that of Western medicine. The induced ovarian cancer model had a high degree of clinical agreement and was similar to human ovarian cancer in terms of tumor growth pattern， disease progression and complications， which is an ideal animal model of ovarian cancer. Although this animal model can simulate the etiology and pathogenesis of ovarian cancer to a certain extent and reflect some indicators of traditional Chinese and Western medicine， it lacks differentiation of traditional Chinese medicine syndromes. ConclusionOn the basis of the original model， the animal model of ovarian cancer was added with Qi deficiency syndrome， blood deficiency syndrome， Qi stagnation syndrome， blood stasis syndrome， heat-toxin syndrome， and Yang deficiency syndrome to establish an animal model combining traditional Chinese medicine disease and syndrome of ovarian cancer， which could better simulate the clinical actual situation of traditional Chinese and Western medicine and lay a solid foundation for the study of integrated traditional Chinese and Western medicine for the treatment of ovarian cancer.