Smoothened inhibition leads to decreased proliferation and induces apoptosis in esophageal adenocarcinoma cells.
The Hedgehog (Hh) pathway is known to be active in Barrett's carcinogenesis. Therefore, we evaluated the efficacy and underlying mechanisms of inhibition of cancer cell growth by the smoothened (Smo) antagonist BMS-833923 in esophageal adenocarcinoma (EAC) cell lines. Cell proliferation and apoptosis were evaluated by flow cytometry, Western blotting, immunofluorescence, and quantitative reverse transcription polymerase chain reactions. Results showed that the Smo antagonist led to reduced Hh pathway activity, resulting in decreased cell proliferation and induction of apoptosis via the intrinsic pathway in the esophageal cancer cells. In conclusion, the Smo antagonist may have application as an EAC chemotherapeutic agent.
Zaidi, AH; Komatsu, Y; Kelly, LA; Malhotra, U; Rotoloni, C; Kosovec, JE; Zahoor, H; Makielski, R; Bhatt, A; Hoppo, T; Jobe, BA
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