Oroxylin A inhibits carcinogen-induced skin tumorigenesis through inhibition of inflammation by regulating SHCBP1 in mice.

Accumulating evidence has shown that SHC SH2 domain-binding protein 1 (SHCBP1) functions as an oncogene and participated in the progression of various cancers. Oroxylin A, an active ingredient extracted from Chinese Medicine Scutellaria baicalensis, shows strong anticancer effects on multiple cancers, however, the pharmacological effect of oroxylin A on skin cancer and the regulatory effect of SHCBP1 on this process have never been evaluated. The present study was aimed at elucidating the effect of oroxylin A on carcinogen (DMBA/TPA)-induced skin tumorigenesis, and to further clarify the role of SHCBP1 in oroxylin A induced antitumor effect. Pretreatment with oroxylin A remarkably inhibited DMBA/TPA-induced tumor formation and growth, and significantly reduced tumor incidence and the average number of tumors per mouse. Oroxylin A suppressed DMBA/TPA-induced skin hyperplasia and tumor proliferation. Oroxylin A significantly inhibited the expression of several inflammatory factors in vivo. In vitro experiments found that oroxylin A inhibited TPA-induced cell malignant transformation of skin epidermal JB6 P + cells. Besides, oroxylin A significantly suppressed the levels of TPA-induced inflammatory factors in vitro. Mechanistic studies showed that oroxylin A remarkably inhibited TPA-induced increased expression of SHCBP1. Overexpression of SHCBP1 attenuated the oroxylin A-induced anti-inflammatory effect. In addition, TPA increased the expression of nuclear NF-κB p65, and SHCBP1 siRNA notably decreased the nuclear NF-κB p65 expression in JB6 P + cells. Collectively, the anti-skin cancer effect of oroxylin A may possibly by inhibiting inflammation via suppression of SHCBP1. Oroxylin A might be a potential candidate compound for the treatment of skin cancer.