Lobaplatin promotes radiosensitivity, induces apoptosis, attenuates cancer stemness and inhibits proliferation through PI3K/AKT pathway in esophageal squamous cell carcinoma.

Radiotherapy is one of the common treatments for esophageal squamous cell carcinoma (ESCC). Yet, local recurrence led by radioresistance is still not solved. Lobaplatin (LBP) is known to have powerful clinical anti-tumor activities in various tumors, but its effect in radiotherapy is rarely studied. Here we report that LBP is a promising radiosensitizer for ESCC. We treated ESCC cells with LBP and radiation, both separately and in combination. Untreated cells were set as control groups. We found that LBP inhibited ESCC cell growth and enhanced their radiosensitivity. LBP also impeded the tumor growth in vivo. LBP combined with radiation significantly increased ESCC cell apoptosis. Meanwhile, LBP obviously decreased the expression of cancer stem cells biomarker CD271 both in vitro and in vivo. The molecular mechanism was related to the downregulation of Bcl-2/Bax ratio, PI3K and p-AKT (Ser473) expression. Taken together, our findings indicated that LBP could enhance the radiosensitivity of ESCC cells by increasing radiation-induced apoptosis, attenuating cancer stemness and inhibiting PI3K/AKT pathway. These results provide a foundation for the combined therapy of radiation and LBP for ESCC in clinical practice.

Preclinical activity of lobaplatin as a single agent and in combination with taxanes for ovarian carcinoma cells.

Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumor types. However, the efficacy of lobaplatin in ovarian cancer has not been systemically evaluated. In this study, lobaplatin as a single agent and in combination with taxanes was investigated in-vitro and in an in vitro model of ovarian carcinoma. Using the sulforhodamine B (SRB) assay, the cytotoxic effects of lobaplatin alone and in combination with taxanes were compared with cisplatin and carboplatin in seven ovarian cancer cell lines. In addition, in-vitro antitumor activities were evaluated with cisplatin-sensitive and cisplatin-resistant human ovarian cancer xenografts in nude mice. The cytotoxicity of lobaplatin was similar to or higher than that of cisplatin and carboplatin, with IC50 values from 0.9 to 13.8 µmol/L in a variety of ovarian cancer cells. The combination of lobaplatin with docetaxel yielded enhanced cytotoxic activity in vitro. In addition, in platinum-sensitive ovarian cancer xenografts, lobaplatin alone showed similar antitumor activity to cisplatin and carboplatin. Furthermore, lobaplatin alone or in combination with docetaxel exhibited significant activity in platinum-resistant ovarian cancer xenografts. These results indicate that the use of lobaplatin alone or in combination with docetaxel might be a rational and novel therapeutic strategy for ovarian cancer. Further clinical development of lobaplatin is clearly warranted.

[Establishment of experimental ventricular septal defect in pigs].

OBJECTIVE: This is a study on the method for establishing experimental animal model of ventricular septal defect(VSD) in pigs. METHODS: Thoracotomy was performed on 15 young pigs under general anaesthesia. A spool-like ring amounted on a specially designed centesis tool was put into right ventricle via an incision on right auricle which was pushed to puncture through the septum. The ring was then left on the septum to create the artificial VSD. 3 days after the operation, echocardiography was conducted to verify the existence of VSDs. The animals were catheterized one month later to obtain hemodynamic data. RESULTS: Ten pigs survived the operation with successful acquisition of VSDs. Doppler echocardiography demonstrated the transseptal shunts with peak velocities ranging from 1.7-4.4 m/sec. Cardiac catheterization showed the Qp/Qs of 1.68-2.12 although the pulmonary pressures remained in normal limits. CONCLUSION: The authors report their experience in the establishment of experimental VSD model in pigs using revised Synhorst method. The preliminary result shows that the VSD model using pigs is feasible and worth improving further in order to provide a useful animal model for the pathophysiological study of intracardiac left to right shunt in the future.