RESUMO
As a first line medicine for malaria treatment, artesunate (ART) also shows antitumor potential. However, little is known about the effect of ART on the cancer cell epithelial-mesenchymal transition (EMT). In this study, we found that ART inhibited cell growth in SK-HEP1 and SM7721 hepatocellular carcinoma cell lines. A microarray was used to identify differentially expressed protein-coding RNAs (pcRNA) and long noncoding RNAs (lncRNA) between SK-HEP1 cells with and without ART treatment. A differentially expressed lncRNA-RP11, the most related to the EMT of liver cancer cells-RP11 was identified by abioinformatics method Overexpressing and silencing assays were used to verify the role of RP11 in cancer cell EMT. The levels of RP11- and EMT-related genes in liver cancer samples from 75 patients were detected by using qualitative polymerase chain reaction or immunohistochemistry. We identified 1334 pcRNAs and 1670 lncRNA with differential expression induced by ART. ART inhibits EMT, proliferation, migration, invasion, and adhesion of liver cancer cells. RP11 depresses the inhibitory effect of ART on cancer cell EMT. The level of RP11 is associated with cancer cell EMT and metastasis and survival rate of the patient. These data suggest that RP11-linking ART and cancer cell EMT are important for ART-inhibited metastasis of liver cancer.
Assuntos
Artesunato/farmacologia , Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , RNA Longo não Codificante/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , RNA Longo não Codificante/genéticaRESUMO
Purpose: Liver cancer is insensitive to chemotherapy. Sorafenib is currently the standard treatment for patients with advanced diseases, with mild survival extension and several intolerable drug-related side effects. The establishment of new treatments is an unmet clinical need. The aim of our study was to assess the efficacy and safety of apatinib, a novel antiangiogenic drug, in the treatment of patients with liver cancer. Materials and Methods: Patients with unresectable or relapsed liver cancer were included in a single center, retrospective, observational study and treated with apatinib until progressive disease or unacceptable toxicity. Results: 32 patients were reviewed from January 2015 to March 2017. No complete response (CR) occurred, 5 patients (16%) showed partial response (PR), 14 patients (44%) had stable disease (SD), 13 patients (41%) had progressive disease (PD), with disease control rate of 60%. Median progression-free survival (PFS) was 5 months (95% confidence interval [CI]: 4.3-6.1 months) for hepatocellular carcinoma (HCC) and 3 months (95% CI: 2.5-4.2 months) for intrahepatic cholangiocarcinoma (ICC). The median overall survival (OS) was 13 months (95% CI: 12.4-14.1 months) for HCC and 5 months (95% CI: 4.5-6.2 months) for ICC, respectively. The most common adverse effects (AEs) were proteinuria (31%), secondary hypertension (28%) and liver dysfunction (13%). Conclusion: Apatinib treatment was an effective for patients with liver cancer. The toxicities were mild and tolerable.