Curcumol improves cisplatin sensitivity of human gastric cancer cells through inhibiting PI3K / AKT pathway

2020 ◽  
Vol 81 (8) ◽  
pp. 1019-1025
Author(s):  
Xiaofei Huang ◽  
Jun Qian ◽  
Lingchang Li ◽  
Xiaozhen Zhang ◽  
Guoli Wei ◽  
...  
2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ruyue Tian ◽  
Hailun Jiang ◽  
Linlin Shao ◽  
Yang Yu ◽  
Qingdong Guo ◽  
...  

Gastric cancer (GC) is one of the most common and fatal malignancies worldwide. MicroRNAs (miRNAs) play a critical role in tumor initiation, proliferation, and metastasis of gastric cancer. miR193b has been identified as a tumor suppressor in a variety of tumor types; however, its role in gastric cancer is yet to be determined. Here, we found a significant downregulation of miR193b expression in both human gastric cancer tissues (p<0.05) and human gastric cancer cell lines (p<0.01). Furthermore, the expression level of miR193b correlated with the tumor type, tumor size, and clinical stage (p<0.05). In vitro, miR193b overexpression inhibited cell survival and induced apoptosis in GC cell lines, indicating that miR193b plays a role in the development of gastric cancer. KRAS was verified as the target of miR193b, and KRAS overexpression attenuated miR193b-induced apoptosis (p<0.05). Moreover, we found that the Akt pathway negatively regulated miR193b, also affecting apoptosis. Further analyses indicated that PIK3CA mutation and KRAS amplification are two mutually exclusive pathways (p<0.01), and we hypothesize that both two pathways could result in the carcinogenic overactivation of KRAS. Thus, our results suggest that the Akt-miR193b-KRAS axis may act as a mechanism affecting apoptosis in gastric cancer cells.


2016 ◽  
Vol 52 (8) ◽  
pp. 857-863 ◽  
Author(s):  
He-Yi You ◽  
Xue-Meng Xie ◽  
Wei-Jian Zhang ◽  
Heng-Liang Zhu ◽  
Fei-Zhao Jiang

Oncogene ◽  
2021 ◽  
Author(s):  
Toshikatsu Tsuji ◽  
Yusuke Maeda ◽  
Kenji Kita ◽  
Kazuhiro Murakami ◽  
Hideyuki Saya ◽  
...  

AbstractFOXO3 is a member of the FOXO transcription factors thought to play a tumor-suppressor role in gastrointestinal cancer, while tumor-promoting function of FOXO3 has also been reported. These results suggest a context-dependent function of FOXO3 in tumor development. However, the relationship between the FOXO3 expression pattern and its role in tumorigenesis has not been elucidated. We examined the FOXO3 expression in 65 human primary gastric cancer and patient-derived xenograft tissues by immunohistochemistry and identified three subtypes according to subcellular localization: FOXO3-nuclear accumulated (FOXO3-Nuc), FOXO3-nuclear/cytoplasmic or cytoplasmic distributed (FOXO3-Cyt), and FOXO3-negative. In the FOXO3-Cyt gastric cancer cells, the expression of the constitutive active mutant FOXO3 (Act-ER FOXO3) induced the nuclear accumulation of FOXO3 and significantly suppressed colony formation and proliferation. The inhibition of the PI3K-AKT pathway by inhibitor treatment also suppressed the proliferation of FOXO3-Cyt gastric cancer cells, which was associated with the nuclear accumulation of endogenous FOXO3. Furthermore, the expression of Act-ER FOXO3 by an endogenous promoter significantly suppressed gastric tumorigenesis in Gan mice, a model of gastric cancer. Finally, treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation. These results indicate that FOXO3 is a latent tumor suppressor for FOXO3-Cyt-type gastric cancer cells and that activation of the PI3K-AKT pathway protects this type of gastric cancer cell from FOXO3-mediated growth suppression via constitutive nuclear export. Thus, the inhibition of the PI3K-AKT pathway and nuclear translocation of endogenous FOXO3 may have therapeutic applications in the treatment of FOXO3-positive and cytoplasmic-type gastric cancer.


2016 ◽  
Vol 55 (12) ◽  
pp. 2236-2246 ◽  
Author(s):  
Hoang-Kieu-Chi Ngo ◽  
Hee Geum Lee ◽  
Juan-Yu Piao ◽  
Xiancai Zhong ◽  
Ha-Na Lee ◽  
...  

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