Radiosensitivity of connexin 43(CX43) on S24-GBMSCs based brain tumor in nude mice / 中华放射肿瘤学杂志

ABSTRACT

Objective:To investigate the impact of connexin 43(CX43) on the connection of S24 glioblastoma multiforme (S24-GBM) cellular network and to explore its role on radio-resistance.Methods:Specific lentiviral vectors were used to knockout CX43 in S24-GBM stem cells (S24-GBMSCs). Alternatively, carbenoxolone (CBX) was used to block transmission of CX43. Subsequently, the animal subjects grafted with S24-GBMSCs were monitored under a multiphoton laser scanning microscope (MPLSM). Dynamic changes of tumor microtubes (TMs) and transmission of Ca 2+ and SR101 in the cellular network were recorded. To study the radiosenstivity of S24-GBM before and after CX43 inhibition, MRI scanning of the brains was taken before and after radiation to assess the tumor sizes. Survival time of each subject was also recorded. Results:In comparison with control group, knockout of CX43 in S24-GBMSCs led to shorter TMs, less TM connected cells, lower Ca 2+ synchronicity and SR101 fluorescence, as well as decreased tumor sizes and prolonged survival time (all P<0.01), which were independent from radiation. However, CBX only demonstrated inhibition on the growth of tumors and the diffussion of Ca 2+ and SR101, without affecting TMs formation. These above-mentioned alterations could be enhanced by the combination of gap43 knockout in S24-GBMSCs with blockage of CX43 by CBX (all P<0.05). Conclusion:CX43 plays a critical role in the radioresistance of S24-GBM by influencing the formation of S24-GBM cellular network and the transmission of important signaling molecules including Ca 2+ and SR101.