Abstract
Gender differences in esophageal cancer patients indicate that estradiol may have antitumor effects on esophageal cancer. The initiation of endoplasmic reticulum stress (ERS) can induce apoptosis in esophageal cancer cells. However, it is still unknown whether estradiol inhibits the development of esophageal cancer by activating ERS pathway. In this study, the gender difference in the development of esophageal cancer was observed by analyzing clinical data and the experimental tumor xenografts in mice. Meanwhile, we investigated the mechanism of ERS in estradiol-mediated inhibition of esophageal cancer using esophageal squamous cell carcinoma cell line EC109. The proportion of male patients with esophageal cancer was significantly higher than female patients. Meanwhile, male patients were prone to have adventitial invasion. The weight of transplanted tumors in female mice was significantly smaller than that in male mice. In vitro experiments showed estradiol inhibits the viability and migration of EC109 cells by increasing the expression of ERS-related proteins, whereas ERS inhibitor 4-PBA abolished the effects of estradiol. In conclusion, our data demonstrate that sex difference exists in the occurrence of esophageal cancer. Estradiol can inhibit the viability and migration of esophageal cancer cells through the activation of ERS, providing a novel insight for esophageal cancer development, treatment, and prevention.
Highlights
Esophageal cancer is one of the eight most common cancers in the world [1], with poor prognosis and low long-term survival [2]
There was no relationship between gender and lymphatic metastasis (P > 0.05) (Figure 1A), but difference was significant in correlation between gender difference and adventitial invasion (P < 0.05) (Figure 1B)
ICI and 4-phenylbutyric acid (4-PBA) enhanced the viability of EC109 cells after treatment with estradiol (Figure 4C). These results suggested that estradiol may inhibit EC109 cell migration and viability, and this inhibition is mediated by endoplasmic reticulum stress (ERS)
Summary
Esophageal cancer is one of the eight most common cancers in the world [1], with poor prognosis and low long-term survival [2]. Esophageal cancers were mainly classified by the tumor–node–metastasis (TNM) grading standard, and surgery is a conventional treatment for most types of esophageal cancer. There are auxiliary treatment methods such as radiotherapy and chemotherapy [3]. Surgery requires high physical conditions of the patients, and the recovery is slow after operation [4]. Radiotherapy and chemotherapy often cause adverse reactions, which affects the function of various tissues and organs of the patients and reduces the repair ability of esophageal mucosa [5]. It is urgent to explore new therapy methods
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