This exploratory proposal is to assess the efficacy of Scutellaria Baicalensis (SB) on preventing ovarian cancer progression and to generate essential preliminary evidence to understand the mechanisms of SB actions. Ovarian cancer is the fifth most commonly diagnosed malignancy in the United States. Due to the late stage at which the disease is usually diagnosed the survival rate is very low and conventional treatment modalities or intervention strategies are usually ineffective. Therefore, the search for efficacious and safe agents to prevent or delay the progression of ovarian cancer remains the top priority in ovarian cancer research. SB is widely used for the treatment of inflammation and cancer in China and in other Asian countries. SB has been shown to have cytotoxic effects on tumors. However, the mechanism responsible for its anticancer effects is still poorly understood. Recently, we observed that SB significantly inhibits growth, causes cell cycle arrest and induces apoptosis in human ovarian cancer cells. Mechanistic studies showed that SB inhibits hypoxia- inducible factor- 1a (HIF-1a) and vascular endothelial growth factor (VEGF) subsequently inhibits tumor cell growth and angiogenesis. Based on these preliminary data, we hypothesize that SB may serve as an efficacious and safe therapeutic agent against ovarian cancer progression by both inducing ovarian cancer cell apoptosis and inhibiting angiogenesis, and that HIF-1a may be a functional target for SB action.
Two aims have been put forth to test the hypothesis:
Specific Aim 1 : Elucidate the mechanism by which SB inhibits HIF- 1a in ovarian cancer cells and inhibits angiogenesis.
Specific Aim 2 : To determine the effect of SB on progression of human ovarian tumors in an orthotopic ovarian tumor model. This proposal will define a highly efficacious and safe chemopreventive agent against ovarian cancer progression, and the findings may result in future clinical investigations to develop SB as a chemopreventive and/or therapeutic agent for ovarian cancer.
The goals of this proposed project are to gain experimental evidence to demonstrate the potent efficacy of Scutellaria Baicalensis (SB) Georgi, in inhibiting the growth and progression of ovarian cancer in an orthotopic ovarian tumor animal model, and to determine the mechanisms by which SB inhibits HIF-1a induced tumor growth and metastasis. The results derived from the proposed studies will provide essential preclinical evidence and mechanistic insights to support the future clinical investigation using this novel chemopreventive agent for effective prevention of ovarian cancer progression. Thus the proposed research will have significant impacts on public health.
|Hussain, Imran; Waheed, Sana; Ahmad, Kashif A et al. (2018) Scutellaria baicalensis targets the hypoxia-inducible factor-1? and enhances cisplatin efficacy in ovarian cancer. J Cell Biochem 119:7515-7524|