The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.
10.1016/S1875-5364(21)60106-1
- Author:
Yao-Dong CHEN
1
;
Fang-Yu CAI
2
;
Yu-Ze MAO
3
;
Yong-Sheng YANG
1
;
Kun XU
1
;
Xiao-Fang LIU
1
;
Wen-Wen FAN
1
;
Wu CHEN
4
;
Feng-Qi JIANG
5
;
Hui ZHANG
6
Author Information
1. Department of Ultrasonic Imaging, the First Hospital of Shanxi Medical University, Taiyuan 030001, China.
2. Department of Thoracic Surgery, the General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin 150088, China.
3. Department of Cardio-Thoracic Surgery, the First Affiliated Hospital of Jiamusi University, Jiamusi 154000, China.
4. Department of Ultrasonic Imaging, the First Hospital of Shanxi Medical University, Taiyuan 030001, China. Electronic address: chenwu@sxmu.edu.cn.
5. Department of General Surgery, Heilongjiang Provincial Hospital, Harbin 150001, China. Electronic address: 15945684810@163.com.
6. Department of Radiology, the First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China. Electronic address: zhang_hui@sxmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Aloperine;
Cervical cancer;
Chemotherapy;
Epithelial-mesenchymal transition;
IL-6-JAK1-STAT3 feedback loop
- MeSH:
Animals;
Apoptosis;
Cell Line, Tumor;
Cell Movement;
Cell Proliferation;
Feedback;
Female;
HeLa Cells;
Humans;
Interleukin-6/genetics*;
Janus Kinase 1;
Mice;
Mice, Nude;
Quinolizidines;
STAT3 Transcription Factor/genetics*;
Signal Transduction;
Uterine Cervical Neoplasms/drug therapy*
- From:
Chinese Journal of Natural Medicines (English Ed.)
2021;19(11):815-824
- CountryChina
- Language:English
-
Abstract:
Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.