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.