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Purpose: Capsid protein L2 is the minor capsid protein of human papillomavirus 16 (HPV16). Although L2-based vaccines were developed, the therapeutic effect of recombinant viral capsid protein L2 (rVL2) was still to be illustrated. Methods: We used glucose uptake and lactate production assay to verify the inhibitory effect of rVL2 on the glucose metabolism in cervical cancer cells. Secondly, we performed gene-chip assay, RT-PCR, and Western blot to determine the role of ITGB7/C/EBPβ signaling pathway in rVL2-mediated glucose metabolism in vitro. Finally, we used an animal model to verify the function of rVL2 in cervical cancer. Results: We found that rVL2 reduced glucose uptake and lactate production levels in cervical cancer cells, which caused the inhibition of cell proliferation. rVL2 decreased the expression levels of key metabolic enzymes, including GLUT1, LDHA, and ALDOA, to affect cell metabolism in cervical cancer cells by inhibiting ITGB7/C/EBPβ signaling pathway in vitro and in vivo. Conclusion: These results demonstrated the vital role of rVL2 in the glycolysis-induced cell growth and proliferation via suppressing ITGB7/C/EBPβ signaling axis. [ABSTRACT FROM AUTHOR]

Abstract: Ovarian cancer is the most malignant gynecologic cancer among women worldwide. Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been identified as a potential therapeutic agent in treating several malignant tumors, but the molecular mechanism of CT in ovarian cancer still remains illustrated. Here, we sought to elucidate the regulatory function of CT on cell glucose metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells effectively inhibited glucose uptake and lactate production in ovarian cancer cells. The expression levels of glycolysis‐related proteins, such as GLUT1, LDHA, and HK2, were decreased by the treatment of CT detected by qRT‐PCR and immunoblotting. Mechanistically, CT exerted its anti‐tumor effect by targeting STAT3/SIRT3/HIF‐1α signaling pathway in vitro and in vivo, which could be rescued by the introduction of SIRT3 shRNA in ovarian cancer cells. The clinical data showed that the expression level of STAT3 in ovarian cancer patients’ sera and tissues was positively correlated with those of GLUT1, LDHA, HK2 and HIF‐1α, but negatively with that of SIRT3These findings provide evidence that CT inhibited cellular glycolysis‐induced cell growth and proliferation through repression of STAT3/SIRT3/HIF‐1α signaling pathway, indicating that CT may be developed as a chemotherapeutic agent to treat ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: The study aims to present the effect of PIK3CA E542K and E545K mutations on glucose metabolism and proliferation and identify their underlying mechanisms in cervical cancer. Methods: The maximum standard uptake value (SUVmax) of tumors was detected by18F-FDG PET/CT scan. In vitro, glycolysis analysis, extracellular acidification rate analysis, and ATP production were used to evaluate the impact of PIK3CA E542K and E545K mutations on glucose metabolism. The expression level of key glycolytic enzymes was evaluated by western blotting and immunohistochemical staining in cervical cancer cells and tumor tissues, respectively. Immunofluorescence analysis was used to observe the nuclear translocation of β-catenin. The target gene of β-catenin was analyzed by using luciferase reporter system. The glucose metabolic ability of the xenograft models was assessed by SUVmax from microPET/CT scanning. Results: Cervical cancer patients with mutant PIK3CA (E542K and E545K) exhibited a higher SUVmax value than those with wild-type PIK3CA (P = 0.037), which was confirmed in xenograft models. In vitro, enhanced glucose metabolism and proliferation was observed in SiHa and MS751 cells with mutant PIK3CA. The mRNA and protein expression of key glycolytic enzymes was increased. AKT/GSK3β/β-catenin signaling was highly activated in SiHa and MS751 cells with mutant PIK3CA. Knocking down β-catenin expression decreased glucose uptake and lactate production. In addition, the nuclear accumulation of β-catenin was found in SiHa cells and tumors with mutant PIK3CA. Furthermore, β-catenin downregulated the expression of SIRT3 via suppressing the activity of the SIRT3 promotor, and the reduced glucose uptake and lactate production due to the downregulation of β-catenin can be reversed by the transfection of SIRT3 siRNA in SiHa cells with mutant PIK3CA. The negative correlation between β-catenin and SIRT3 was further confirmed in cervical cancer tissues. Conclusions: These findings provide evidence that the PI3K E542K and E545K/β-catenin/SIRT3 signaling axis regulates glucose metabolism and proliferation in cervical cancers with PIK3CA mutations, suggesting therapeutic targets in the treatment of cervical cancers. Trial registration: FUSCC 050432–4-1212B. Registered 24 December 2012 (retrospectively registered). [ABSTRACT FROM AUTHOR]