Mechanism for Regulation of Melanoma Cell Death via Activation of Thermo-TRPV4 and TRPV2

Figure 4

Silencing TRPV4 ion channel suppressed GSK1016790A mediating signals. (a) A representative western blot indicated the successful knockdown of TRPV4 protein by shRNA (i) & (ii). (b) Loss of TRPV4 fully suppressed the inhibition of proliferation for the treatment of GSK1016790A (1 nM, 10 nM, 20 nM, and 50 nM) to A375 melanoma cells. (c) Suppression of TRPV4 attenuated the inhibition of proliferation for the treatment of 4α-PDD (100 nM, 200 nM, 400 nM, and 1 μM) in A375 melanoma cells. (d) Inhibition of TRPV4 by GSK2193874 (10 nM, 50 nM, 100 nM and 200 nM) did not affect melanoma cell proliferation. (e) Treatment with GSK1016790A (1 nM, 10 nM, 20 nM and 50 nM) and GSK2193874 (100 nM) did not affect cell viability of melanoma. (f) Pretreatment of ruthenium red fully suppressed the inhibition of proliferation for the application of GSK1016790A with 20 nM and 50 nM to A375 melanoma cells. All tests were performed in at least three independent experiments.

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