Cyclopamine Suppresses Human Esophageal Carcinoma Cell Growth by Inhibiting Glioma-Associated Oncogene Protein-1, a Marker of Human Esophageal Carcinoma Progression

Abstract

Background Esophageal carcinoma is a common gastrointestinal tumor in humans. Cyclopamine, a Hedgehog (Hh)-pathway-specific inhibitor, is an effective chemotherapeutic drug for suppressing tumor cell differentiation, with unclear mechanisms. We investigated glioma-associated oncogene protein-1 (Gli-1) expression in human esophageal carcinoma tissue and the inhibition of cyclopamine on EC9706 esophageal carcinoma cell growth. Material/Methods Gli-1 in tumor tissue was measured by immunohistochemistry (IHC). EC9706 cells were treated with different concentrations of cyclopamine and incubated for different times. MTT method, flow cytometry, and Acridine orange/ethidium bromide (AO/EB) double-fluorescence staining were applied to detect cell proliferation and apoptosis. Western blot (WB) analysis was performed to assess Gli-1 expression. Results Gli-1 was associated with patient age, gender, lymphatic metastasis, tumor recurrence, and stage, with significantly ( P <0.05) positive correlations with age, lymphatic metastasis, tumor recurrence, and stage. At 12 h ( F =214.57), 24 h ( F =76.832), 48 h ( F =236.90), and 72 h ( F =164.55), the higher the concentration of cyclopamine, the higher the inhibition rate of suppressing EC9706 proliferation, and this effect was significant ( P <0.05). The number of early-apoptosis cells increased as the concentration of cyclopamine increased. Morphology of EC9706 cells appeared as round with rough edges, karyopyknosis, and karyorrhexis. After 48 h, apoptosis rates of EC9706 cells treated with different concentrations of cyclopamine were (7.73±1.25)% at 2.5 μM, (13.37±1.42)% at 5.0 μM, (22.3±2.92)% at 10.0 μM, and (33.57±1.75)% at 20.0 μM, and the effect was dose-dependent. Gli-1 was obviously reduced after cyclopamine treatment and the effect was dose-dependent. Conclusions Gli-1 is highly expressed in human esophageal carcinoma, and could be a marker for use in assessing tumor stage and the deciding on treatment target.

Environmental Cadmium Exposure Promotes the Development, Progression and Chemoradioresistance of Esophageal Squamous Cell Carcinoma

“…The human ESCC cell lines EC109 and EC9706 were gifts from Dr. Jing Yu and Dr. Xianbin (Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, China) (Peng et al, 2020;Yu et al, 2019). Cells were maintained in RPMI-1640 medium (HIMEDIA, Mumbai, India) with 10% fetal bovine serum (FBS; HyClone, Logan, UT, United States) in an atmosphere of 5% CO 2 at 37 °C.…”

Porphyromonas gingivalis secretion leads to dysplasia of normal esophageal epithelial cells via the Sonic hedgehog pathway

“…A large number of studies showed the SHH pathway to be silent in normal mature esophageal epithelial cells, but in dysplasia and cancer, the SHH pathway is activated ( Zhu et al., 2011 ; Okumura et al., 2014 ; Wadhwa et al., 2017 ). The SHH pathway inhibitor, CPM, has been used in the clinical treatment of cancer ( Berman et al., 2003 ; Yu et al., 2019 ). We previously confirmed that SHH can regulate the proliferation and differentiation capacity of mouse esophageal epithelial cells.…”

MGFFCNN: Two‐dimensional matrix spectroscopy combined with multi‐channel gradient feature fusion convolutional neural network means to diagnose glioma and esophageal cancer patients

“…Aberrant activation of the glioma‐associated oncogene Gli‐1 is a key factor in the hippocampal signaling pathway, and this gene also plays an inhibitory role in the growth of EC 9706 esophageal cancer cells and so on. [ 24 ] Gene expression in glial carcinoma and esophageal carcinoma has some similarity. In order to accurately distinguish glioma and esophageal cancer and improve patients' survival rate, we attempt to develop a rapid, nondestructive, and sensitive method that is based on molecular vibrational spectroscopy to distinguish the two tumor diseases.…”