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Objective: This study aimed to investigate the radiosensitivity of bortezomib to cervical cancer and the possible underlying mechanism., Methods: HeLa and SiHa cell lines with or without hypoxia treatment were divided into control, radiation alone, bortezomib alone, and radiotherapy plus bortezomib groups. CCK8 assay, clone formation assay, flow cytometry, and immunofluorescence test were used to measure cell proliferation, colony formation, apoptosis, and DNA double-strand break (DSB). Western blot analysis was performed to detect the expression of HIF-1α, PARP-1, and caspase-3, -8, and -9., Result: Statistical analysis of data revealed that bortezomib at nanomolar level exerted a radiosensitization effect on both cervical cancer cell lines in normoxia or hypoxia. Western blot analysis showed that the drug could inhibit hypoxia-related HIF-1α expression to increase apoptosis-related caspase-3, -8, and -9 activation and DNA DSB-related PARP-1 cleavage., Conclusions: Radiotherapy sensitization of bortezomib on cervical cancer cell lines had a drug-dose relation, and sensitization in hypoxia was more remarkable than in normoxia. Bortezomib may be a potential radiotherapy sensitization drug for cervical cancer.

Objective: Lung cancer remains the leading cause of cancer-related death worldwide and microRNAs (miRNAs) play important roles in lung cancer progression. In this study, we investigate the effects of miR-132/212 cluster on the growth of subcutaneous xenografts of human lung cancer H1299 cells in nude mice, and further explore the underlying mechanisms., Methods: Nude mice with subcutaneous transplantation tumor of human lung cancer H1299 cells were randomly divided into three groups: the sham group, the control vector group, and the microRNA-132/212 group. The control vector and microRNA-132/212 cluster plasmid was intratumoral injected respectively. Tumor volume was measured during the intervention process, with a tumor growth curve generated. Immunohistochemistry was performed to analyze the expression level of Ki-67, P21, CyclinD1 and CD31 in each group., Results: The tumor volume of miR-132/212 group was significantly smaller than that of the control group at the terminal time point (P < 0.05). The expression levels of Ki-67, CyclinD1 and CD31 in the miR-132/212 group was significantly lower than the control group (P < 0.05), while the expression levels of P21 in the miR-132/212 group were significantly higher than the control group (P < 0.05)., Conclusion: miR-132/212 cluster significantly inhibited the growth of subcutaneous xenografts of human lung cancer H1299 cells in nude mice. The inhibitory effect of miR-132/212 cluster in tumor growth may be mediated by upregulating the expression of P21 and downregulating the expression of CyclinD1, thereby inhibiting tumor tissue proliferation and angiogenesis and resulting in the inhibition of tumor growth.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.