Abstract
Paclitaxel has been generally used to treat primary and metastatic esophageal carcinoma. It has been shown that nestin is highly expressed in esophageal carcinoma and that there is a strong association of nestin expression with poor prognosis in esophageal carcinoma patients. In this study, using immunohistochemistry, in situ hybridization and Western blotting we demonstrated that nestin was overexpressed in the invasive esophageal carcinoma. To further elucidate whether nestin inhibition could enhance paclitaxel sensitivity to esophageal carcinoma cells, we applied nestin siRNA in esophageal squamous cell carcinoma Eca-109 cells. Flow cytometry and TUNEL staining both showed that combination of paclitaxel treatment and nestin knockdown resulted in greater induction of apoptosis of esophageal carcinoma cells as compared with the cells transfected with control siRNA (also treated with paclitaxel). This study indicates that nestin knockdown enhances chemotherapeutic sensitivity of paclitaxel to esophageal carcinoma, and suggests that silencing of nestin could be a valuble therapeutic approach for enhancing drug sensitivity and thereby improving the treatment outcome of esophageal carcinoma patients.
Highlights
IntroductionSurgery is the primary treatment, but the 5-year survival of patients with metastatic esophageal carcinoma managed with surgery remains poor, less than 20–40% [2]
Esophageal carcinoma is the eighth most frequent malignant tumors worldwide [1]
It has been shown that nestin is highly expressed in esophageal carcinoma and that there is a strong association of nestin expression with poor prognosis in esophageal carcinoma patients
Summary
Surgery is the primary treatment, but the 5-year survival of patients with metastatic esophageal carcinoma managed with surgery remains poor, less than 20–40% [2]. Paclitaxel, a microtubule-stabilizing drug, has been widely used as a single agent or in combination therapy with other chemotherapeutic agents to treat primary and metastatic esophageal carcinoma [5]. Esophageal carcinoma is generally insensitive to anticancer drugs, which makes chemotherapeutic treatment difficult in the clinic. Discovery of the mechanisms underlying drug resistance is of great importance in the development of new strategies for treatment of drugresistant tumors. Increased repair of drug-induced DNA damage, blocked apoptosis, disruptions in the signal pathways, and alterations of factors involved in cell cycle contribute to the development of drug-resistance. It has been shown to contribute to drug resistance in P-glycoprotein-dependent manner [9]
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