Abstract
The overall five-year survival rate for patients with esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages. Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on tumor cells. However, the mechanisms by which RTP confer these effects and its importance in esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP’s effects on tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2, caspase-3, caspase-9, and PCNA in CE81T/VGH cells or the tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that tumor size, tumor weight, and proliferating cell nuclear antigen protein expression in tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax proteins, while inhibiting the expression of Bcl-2 in cancer cells. In addition, RTP significantly increases the expression of cleaved caspase-9 and cleaved caspase-3 proteins in tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as caspase-9 and caspase-3.
Highlights
Esophageal cancer is characterized as a highly malignant tumor
There are two main histopathological subtypes of esophageal cancer: squamous cell carcinoma and adenocarcinoma, with the former being the dominant form in Asia and Africa [1,2]
Esophageal squamous cell carcinoma (ESCC) is caused primarily by smoking and the consumption of alcohol and hot beverages, while adenocarcinoma is associated with obesity, smoking, and gastroesophageal reflux disease
Summary
Esophageal cancer is characterized as a highly malignant tumor. According to the World Health Organization’s 2020 statistics, esophageal cancer is the sixth leading cause of cancer-related deaths and the seventh most common cancer worldwide [1]. There are two main histopathological subtypes of esophageal cancer: squamous cell carcinoma and adenocarcinoma, with the former being the dominant form in Asia and Africa [1,2]. The overall five-year survival rate for people with esophageal cancer is less than 20% [1]. Patients often develop resistance to the drugs or suffer side effects, shortening the five-year survival rate to a mere 15–25% [7,8]. Against this backdrop, there is a pressing need to develop effective drugs with minimal side effects for the treatment of esophageal cancer
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