Antiproliferative Effects of Matricine in Gemcitabine-Resistant Human Pancreatic Carcinoma Cells Are Mediated via Mitochondrial-Mediated Apoptosis, Inhibition of Cell Migration, Invasion Suppression, and Mammalian Target of Rapamycin (mTOR)-TOR/PI3K/AKT Signalling Pathway
Authors: Li Wang
LuJia Chen
Kaifeng Fang
Zhi Fang
Tao Liu
Journal: Medical Science Monitor (2019)
Discipline: CLINICAL MEDICINE
Keywords: Pancreatic cancer; matricine; anticancer effects; apoptosis; caspases
Affiliations: Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland), Department of Digestive Tumor Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China (mainland)

Abstract:  BACKGROUND Pancreatic cancer is a major cause of mortality worldwide. Inefficient drugs, their adverse effects, and the development of drug resistance make it difficult to curb the growing incidence of pancreatic cancer. Against this backdrop, the development new drug regimens with no or negligible adverse effects is imperative. We assessed the anticancer effects of a plant-derived sesquiterpene - matricine - against capan-2 pancreatic cancer cells. MATERIAL AND METHODS Cell viability was determined by MTT assay. AO/EB, DAPI, and annexin V/PI staining were used to detect apoptosis. Transwell assays were used for monitoring of cell migration and invasion. Immunoblotting was used to examine the expression of proteins. RESULTS The results showed that matricine halted the proliferation of capan-2 cells, with minimal toxic effects on normal pancreatic cells. The anticancer effects were due to the induction of apoptotic cell death, which was allied with activation of caspases 3 and 9, upregulation of Bax, and downregulation of Bcl-2. Moreover, matricine suppressed the migration and invasive abilities of pancreatic cancer cells at IC50. We also assessed the effects of matricine on the mTOR/PI3K/AKT signalling pathway. We found that matricine efficiently blocked this pathway, suggesting the anticancer potential of matricine. CONCLUSIONS Matricine induced antiproliferative effects in capan-2 human pancreatic cancer cells through inducing apoptosis, caspase activation, inhibition of cell migration and invasion, and blocking the mTOR/PI3K/AKT signalling pathway. 

Retracted: Yes

PubPeer comments:
 *[right]* Figure 8 from [Fang et al (2019)] .  Effect of matricine on mTOR PI3K AKT signalling pathway at indicated concentrations of matricine. *[left]* Figure 8 from [Zeng et al (2018)] .  Western blot analysis demonstrated the effect of indicated concentrations of CAE on expression of mTOR PI3K AKT signaling pathway proteins. ![file] Green and rectangles marks bands also found in *[right]* Fig 7 from [Wang et al (2018b)] .  Effect of farnesol on the expression of PI3K Akt proteins in HeLa human cervical cancer cells. After treating the cells with 0, 10, 50 and 150 u00b5M dose of farnesol, the expression levels of different proteins were evaluated by western blot assay . *[left]* Fig 9 from [Wang et al (2018a)] .  Effect of boswellic acid on protein expression of PI3K AKT pathway in HCT-116 cells as indicated by western blotting . ![file] , 
 *[right]* Figs 6 and 7 from [Fang et al (2019)] .  Effect of matricine on the migration of capan-2 cells. ...  Effect of matricine on the invasion of capan-2 cells . *[left]* Figure 6C from [Sun et al (2019)] .  Gfi1 overexpression rescues the effects of miR-650 inhibition on the proliferation migration and invasion of SCC-25 cells. Effect of Gfi1overexpression (pcDNA-Gfi1) on ... (C) migration and invasion of NC or miR-650 inhibitor transfected SCC-25 cells. ![file] UPDATE: Figure 5 from [Yang, Cai Zhao (2020)] .  A: Cell migration and B: Invasion of miR-NC and miR-1 mimics transfected MBA-MD-231 cells. ![file] , 
 *[left]* Figure 2.  DAPI staining showing the apoptosis-inducing effect of matricine on capan-2 cell . *[right]* Figure 5 from [Wang et al (2019)] .  DAPI staining images showing induction of apoptosis by Acetylshikonin on the KB-R images. Apoptosis was confirmed by DAPI staining which showed apparent changes in the nuclear morphology (chromatin condensation and nuclear fragmentation) of the KB-R cells . ![file] Overlaps marked. , 
 Retracted [25 March 2021] .  An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. ,