Mechanism of Proguanil Enhancing the Inhibitory Effect of Sotorasib on Proliferation and Migration of KRASG12C Wild-type Bladder Cancer Cells

ZHANG Zhirong; WANG Weifan; XIAO Di; YANG Xiaoping

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Journal of Hunan Normal University(Medical Science) ›› 2023, Vol. 20 ›› Issue (6) : 9-13.

Mechanism of Proguanil Enhancing the Inhibitory Effect of Sotorasib on Proliferation and Migration of KRAS^G12C Wild-type Bladder Cancer Cells

ZHANG Zhirong, WANG Weifan, XIAO Di, YANG Xiaoping

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Abstract

Objective To explore whether proguanil can enhance the sensitivity of KRAS^G12C wild-type bladder cancer cells to sotorasib and its mechanism. Methods MTT, clone formation assay and Compusyn software were used to test whether the combination of sotorasib and proguanil can enhance the inhibition of KRAS^G12C wild-type bladder cancer cell proliferation and how the combined effect is. Scratch experiment was used to detect the inhibitory effect on cell migration, and finally, WB experiment was used to detect the inhibitory effect on proliferation related proteins. Results Sotorasib combined with proguanil enhanced the inhibition of proliferation and migration of KRAS^G12C wild-type bladder cancer cells. And the inhibitory effect on the expression of proliferation related proteins such as p-cRAF and p-ERK was enhanced. Conclusion Proguanil can enhance the sensitivity of KRAS^G12C wild-type bladder cancer cells to sotorasib by inhibiting RAF/ERK pathway.

Key words

wild-type bladder cancer cells / KRAS^G12C / proguanil / sotorasib / proliferation / migration / mechanism

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ZHANG Zhirong, WANG Weifan, XIAO Di, YANG Xiaoping. Mechanism of Proguanil Enhancing the Inhibitory Effect of Sotorasib on Proliferation and Migration of KRAS^G12C Wild-type Bladder Cancer Cells[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(6): 9-13

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