Scutellaria baicalensis is an anti-inflammatory and antineoplastic Chinese herbal therapy. We have previously shown that S. baicalensis can inhibit hepatocellular carcinoma (HCC) cell growth in vitro. In this study, we sought to determine the effect of S. baicalensis on the cell signaling network using our newly developed Pathway Array technology, which screens cell signaling pathways involved in cell cycle regulation. The HCC cell line (HepG2) was treated with S. baicalensis extract in vitro. The effect on the cell cycle was analyzed by flow cytometry, and the expression of various signaling proteins was assayed with Pathway Array. Our results indicate that S. baicalensis exerts a strong growth inhibition of the HepG2 cells via G(2)/M phase arrest. The Pathway Array analysis of 56 proteins revealed a total of 14 differentially expressed proteins or phosphorylations after treatment. Of these, 9 showed a dose-dependent decrease (p53, ETS1, Cdc25B, p63, EGFR, ERK1/2, XIAP, HIF-2alpha, and Cdc25C) whereas one demonstrated a dose-dependent increase (Cyclin E) after treatment with 200 microg/ml of S. baicalensis. Using computer simulation software, we identified additional hubs in the signaling network activated by S. baicalensis. These results indicate that S. baicalensis exerts a broad effect on cell signaling networks leading to a collective inhibition of cell proliferation.

Lung cancer, specifically non-small cell lung cancer (NSCLC), is a leading cause of mortality worldwide. In China, a dramatic increase in the incidence of NSCLC is expected in the next 20 years (Molina et al. Mayo Clin Proc. 2008;83:584–594). Mutated epidermal growth factor receptor (EGFR) status is a known predictor of response to tyrosine kinase inhibitors (TKIs), and immunohistochemistry may be a less costly way of predicting presence of mutation. In this study, mutation analysis of EGFR in 218 cases of NSCLC was performed. One hundred thirty tissue samples were examined via immunohistochemistry of p-EGFR (Y1045 and Y1068) and correlated with mutation status. Mutations were seen in 29% of patients, and were correlated with female sex, nonsmoking history, and adenocarcinoma histology. Phosphorylation at Y1045 was noted in 52% of cases, but in 71% of cases with EGFR mutation (P = .003). Phosphorylation of Y1068 was seen in 55% of cases but in 73% of cases with EGFR mutation (P = .006). This study correlating EGFR mutation with p-EGFR expression in resected NSCLC is one of the largest to date, although TKI response could not be assessed. The data show that, among Chinese patients, detection of p-1045 and p-1068 expression with immunohistochemistry predicts EGFR mutations. Immunohistochemical analysis of p-EGFR may be useful to predict responses to TKI therapy, although future studies are necessary.

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