No abstract

This study investigates the antitumor effects and functional mechanism of resveratrol-bovine serum albumin nanoparticles (RES-BSANP) on human primary ovarian carcinoma cells in nude mice. An implanted tumor model was established by injecting a suspension of the human primary ovarian cancer cell SKOV 3 into the subcutaneous tissue of nude mice. The tumor-bearing mice (n ¼ 32) were randomly divided into 8 groups, which received intraperitoneal injections of normal saline (0.9%, 0.5 mL), BSA (1.5 mg/kg, 0.5 mL), or RES-BSANP or RES (200, 100, and 50 mg/kg, 0.5 mL), respectively, once a week for 4 weeks. The in vivo antitumor efficacy was evaluated by measurement of tumor volume, whereas morphological alterations were observed by transmission electron microscope (atomic force microscopy); TUNEL assays and immunoblotting for apoptotic and cell proliferation proteins were carried out to elucidate the possible mechanism. RES-BSANP was found to exhibit certain highly desirable characteristics such as innocuity, better dispersity, and water solubility; it affected the in vivo tissue/organ distribution of RES in a remarkable manner. The administration of RES-BSANP significantly retarded the growth of carcinomas in nude mice from the third week onwards, and the inhibition rate was markedly higher than in mice treated with RES (52.43% vs. 46.34%, p < 0.05), without causing weight loss ( p > 0.05). Simultaneously, apoptotic and necrotic morphological characteristics were observed with electron microscopy in the tumor tissues of treated mice. TUNEL staining revealed that the tumors from RES-BSANPtreated mice exhibited a similar apoptotic index as RES control tumors. Western blot analysis of the protein expression profiles revealed that part of the mechanism may be mediated by triggering the release of cytochrome c from the intermembrane space and upregulating the expression of caspase-9 and caspase-3, suggesting that the mitochondrial apoptotic pathway was being activated.

Ovarian cancer is the most lethal gynecologic malignancy among women and usually initiated by the malignant transformation of epithelial cells. The progression of ovarian cancer involves a cascade of events, including tumor cell epithelial-mesenchymal transition (EMT), invasion, migration, and angiogenesis. Slug plays vital roles in the development of motile and invasive manner of cancer cells via EMT progression. The present work is devoted to investigate the effect of slug on the invasion and angiogenesis in ovarian cancer. The findings reveal that tumors with high expression of slug (44 of 60) represent higher tumor grade, lymph node metastasis, and worse prognosis than those with low expression (16 of 60; P < .05). We also identified a significant correlation between the slug and the microvessel density (MVD). Results of transwell migration assay showed that decreased slug induced by short hairpin RNA contributed to the repressed invasion and migration of SKOV3 cells. Additionally, the migration and tube formation capacity of human umbilical vein endothelial cells were markedly decreased in SKOV3-sh-conditioned medium compared to SKOV3 and SKOV3-NC. Furthermore, xenograft mouse models (SKOV3/SKOV3-sh cells injection into BALB/c nude mice) were developed to validate the effects of slug. The data confirmed that inhibited expression of slug extensively decreased the growth of tumor and MVD in vivo. Moreover, knockdown of slug can significantly reduce tumor angiogenesis of SKOV3 cells via ccn1/vascular endothelial growth factor. Thus, our present study demonstrates that slug is closely associated with tumor metastasis and angiogenesis in ovarian cancer.

Background: Electroacupuncture (EA), a treatment derived from traditional Chinese medicine, can effectively improve hyperandrogenism and insulin resistance in patients with polycystic ovary syndrome (PCOS), however, its underlying mechanisms remain obscure. This study aimed to investigate whether EA could mitigate PCOS-like symptoms in rats by regulating autophagy. Methods: A rat model of PCOS-like symptoms was established by subcutaneous injection with dehydroepiandrosterone (DHEA), and then EA treatment at acupoints (ST29 and SP6) was carried out for 5 weeks. To inhibit autophagy in rats, intraperitoneal injection with 0.5 mg/kg 3-MA (an autophagy inhibitor) was performed at 30 min before each EA treatment. Results: EA intervention alleviated PCOS-like symptoms in rats, which was partly counteracted by the combination with 3-MA. Moreover, DHEA-exposure-induced deficient autophagy in skeletal muscle was improved by EA treatment. EA-mediated improvements in insulin resistance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in PCOS-like rats were counteracted by 3-MA pretreatment. Mechanically, EA attenuated autophagy deficiency-mediated insulin resistance in PCOS-like rats via inactivating mTOR/4E-BP1 signaling pathway. Conclusions: Taken together, our findings indicate that EA treatment ameliorates insulin resistance, mitochondrial dysfunction, and ER stress through enhancing autophagy in a PCOS-like rat model. Our study provides novel insight into the mechanisms underlying the treatment of EA in PCOS, which offers more theoretic foundation for its clinical application.