RESUMO
Renal cell carcinoma (RCC) is a common type of kidney cancer that lacks effective therapeutic options. Ginsenoside compound K (CK), an active metabolite of ginsenosides, has been reported to induce apoptosis in various types of cancer cells. However, the effects of CK in RCC remain to be elucidated. Thus, the aim of the present study was to investigate the antitumor effects of CK on RCC cells. The effects of CK on the proliferation, migration, invasion, cell cycle and apoptosis of RCC cell lines (Caki1 and 768O) were investigated using MTT, wound healing, Transwell and flow cytometry assays, respectively. Changes in the expression levels of long noncoding RNAs (lncRNAs) and proteins were measured via reverse transcriptionquantitative PCR and western blotting, respectively. Transfections with testis associated oncogenic (THOR) small interfering RNA and pcDNA were performed to knock down and overexpress lncRNA THOR, respectively. It was found that CK could effectively inhibit the proliferation, migration and invasion of RCC cells. CK also induced cell cycle arrest and caspasedependent apoptosis in RCC cells. Furthermore, the generation of reactive oxygen species and inhibition of the lncRNA THOR played important roles in the antitumour effects of CK in RCC cells. The present data revealed that CK was a potent antitumour agent against RCC.
Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Ginsenosídeos/farmacologia , Neoplasias Renais/tratamento farmacológico , RNA Longo não Codificante/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ensaios de Seleção de Medicamentos Antitumorais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/uso terapêutico , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , RNA Longo não Codificante/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of present study was to examine whether metformin in association with quercetin has any synergistically anti-tumor effects on prostate cancer. Our findings showed that metformin in combination with quercetin synergistically inhibited the growth, migration and invasion of both PC-3 and LNCaP cells. Co-treatment of these two agents induced more apoptosis than single agent treatment. The co-treatment-induced apoptosis was caspase-dependent and accompanied by the down-regulation of Bcl-2 family members. Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway. Moreover, these two agents acted synergistically to repress the growth of human prostate cancer cell xenograft in vivo in nude mice. In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway. Thus, combination treatment of metformin and quercetin would be a promising therapeutic strategy for prostate cancer patients.
