Modified 5-aminolevulinic Acid Photodynamic Therapy (M-PDT) Inhibits Cutaneous Squamous Cell Carcinoma Cell Proliferation Via Targeting PP2A/PP5-mediated MAPK Signaling Pathway

Background: We previously demonstrated that M-PDT is painless and effective in precancerous skin diseases treatment. However, whether M-PDT is effective in cSCC and the underlying inhibitory mechanism remains enigmatic.

Objective: We aims to unveil the effect of M-PDT on cSCC cell proliferation and the regulatory effect of M-PDT on MAPK signaling.

Methods: The proliferation and migration of cSCC cells were revealed by CCK8 assay, tumor sphere formation assay and scratch assay respectively. The expression of MAPKs was examined by western blot. The activity of PP2A and PP5 was regulated by inhibitor and recombinant adenoviruses.

Results: Here, we show that M-PDT inhibits cSCC cell proliferation by activating p-JNK, p-p38 and inhibiting p-Erk1/2, as well as activation of PP2A and inactivation of PP5. Furthermore, pharmacological inhibition of PP2A conferred resistance to M-PDT's suppression on p-Erk1/2 and attenuated inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP2A showed the contrary results. Pharmacological inhibition of PP5 potentiated M-PDT's elevation on p-JNK and strengthened inhibitory effects of M-PDT on cell proliferation whereas overexpression of wild-type PP5 exhibited the contrary results.

Conclusion: Our findings indicate that M-PDT inhibits cSCC cell proliferation via targeting PP2A/PP5-mediated MAPK signaling pathway.