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 SKOV3 into the
subcutaneous tissue of nude mice. The tumor-bearing mice (n¼32) 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 50mg/kg, 0.5mL), 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.
Liyuan Guo,Yan Peng,Jingping Yao,Lihua Sui,Anxin Gu,Jing Wang
Cancer Biotherapy & Radiopharmaceuticals