Involvement of TRPV1 and TRPV4 Channels in Enhancement of Metastatic Ability Induced by γ-Irradiation in Human Lung Cancer A549 Cells
BPB Reports(2020)
摘要
Radiation therapy is an important local treatment for malignant tumors, but ionizing radiation may also facilitate tumor invasion and metastasis. The transient receptor potential (TRP) superfamily, which is a diverse group of ion channels activated by various stimuli, has a variety of pathophysiological functions, including a role in malignancy. However, it is not clear whether TRP channels influence radiation-induced biological effects. Here, we show that TRPV1 and TRPV4 channels contribute to the γ-irradiation-induced enhancement of migration of human lung cancer A549 and mouse melanoma B16 cells. We found that γ-irradiation induced both cell migration and actin stress fiber formation of A549 cells, but both effects were suppressed by the TRPV1 inhibitors capsazepine AMG9810, SB366791, and BCTC, and by the TRPV4 inhibitors RN-1734 and GSK2193874. γ-Irradiation induced migration was also suppressed by knockdown of TRPV1 and TRPV4 channels. Furthermore, γ-irradiation of B16 mouse melanoma cells increased the number of lung metastases in C57BL/6 mice, compared to non-irradiated B16 cells, and TRPV1 and TRPV4 channel inhibitors suppressed this increase. These results suggest that TRPV1 and TRPV4 channels are potential targets for intervention to block the acquisition of motility by cancer cells during radiotherapy in order to reduce the risk of metastasis.
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