Abstract
To investigate the regulatory effect of curcumin on expression of signal transducer and activator of transcription 3 (STAT3) in skin squamous cell carcinoma tissues as well as possible mechanisms of curcumin in prevention and treatment of skin squamous cell carcinoma. Highly invasive A431 cells were treated with curcumin at various doses .The cytotoxic effects of treatment with 5, 10, 15, 20, 25, 30, 35, 40 and 50 umol/L curcumin for 24, 48 and 72 hours on A431 cells were measured by MTT assay. The invasion capacity of cells treated with 5, 10 and 15 umol/L curcumin was measured by Transwell test, while adhesive ability was assessed by cell adhesion assay. The effects of 5,10 and 15 umol/L curcumin on expression levels of STAT3 were determined by Western blotting and on transcription levels of STAT3 mRNA by RT-PCR. Treatment with curcumin at a doses of more than 15 umol/L for more than 24 hour inhibited the growth of A431 cells in a time-and dose-dependent fashion (p<0.001). The doses of 15 umol/L and less for 24 hours showed no significant cytotoxic effects on the cells, survival rates being more than 85%.The invasion and adhesive abilities decreased gradually with the increasing curcumin concentration, 15 umol/L exerting the strongest inhibitory effects (p<0.05). Curcumin showed significant dose-dependent inhibitory effects on the transcription level of STAT3 mRNA (p<0.05). Curcumin may reduce the invasive ability of A431 cells by inhibiting the activation of STAT3 signal pathway and expression of STAT3 as a target gene in the pathway.
Highlights
In the past 30 years, the morbidity and mortality of cancer has been demonstrating a growing trend (Kraljik et al, 2014; Qian et al, 2014)
The cell viability of MTT detection When the concentration of curcumin is more than 15 umol/L, the action time was more than 24h, the growth inhibition of cells in a time and dose dependence, and the difference was statistically significant (p 85%( Table
Cutaneous squamous cell carcinoma is higher incidence rate of malignant skin tumors, which occupies a great proportion in the skin malignant tumor occurrence and ultraviolet radiation, the skin squamous cell carcinoma is closely related with the environment, and the destruction of the ozone layer increased, its incidence has been rising trend, generally 80% to 90%, especially in the elderly
Summary
In the past 30 years, the morbidity and mortality of cancer has been demonstrating a growing trend (Kraljik et al, 2014; Qian et al, 2014). Signal transducer and activator of transcription factor 3 (STAT3) is a key molecule in various oncogenic signaling pathway, the downstream regulation of many growth, and tumor cell apoptosis, angiogenesis and metastasis related key points, such as CyclinD1, Survivin, Bcl-2, MMP2, STAT3 involved in cell growth (Chen et al, 2013), differentiation, division and development of many physiological process, and plays an important role in the malignant transformation of cells( Qu et al, 2013). Focusing multiple oncogenic tyrosine kinase signal channel, in a variety of tumor cells and tissues have had multiple activation, abnormal expression of key genes in STAT3 after the induced activation of the cell proliferation and differentiation, survival, apoptosis, closely related, through various channels to promote cell proliferation, malignant transformation, impede apoptosis expression of carcinogenesis, so at present is defined as a cancer gene
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