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. 2019 Apr 21:25:2943-2949.
doi: 10.12659/MSM.914244.

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

Kaifeng Fang  1 , Li Wang  1 , LuJia Chen  1 , Tao Liu  2 , Zhi Fang  1
Affiliations

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

Kaifeng Fang et al. Med Sci Monit. .

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.

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Conflict of interest statement

Conflict of interest

None.

Figures

Figure 1
Figure 1
(A) Chemical structure of matricine. MTT assay showing the effect of matricine on the viability of (B) pancreatic capan-2 cells and (C) HTRET-HPNE non-cancerous cells. The experiments were performed in triplicate and results are shown as mean ±SD (* P<0.05).
Figure 2
Figure 2
DAPI staining showing the apoptosis-inducing effect of matricine on capan-2 cells. The experiments were performed in triplicate. The figure shows that matricine induces apoptosis in capan-2 cells in a concentration-dependent manner.
Figure 3
Figure 3
AO/EB staining showing the apoptosis-inducing effect of matricine on capan-2 cells. The experiments were performed in triplicate. The figure shows that matricine triggers apoptosis in capan-2 cells in a concentration-dependent manner.
Figure 4
Figure 4
Annexin V/PI staining showing the percentage of apoptosis in matricine-treated capan-2 cells. The experiments were performed in triplicate. The figure shows that the apoptotic cell populations increased with increased concentration of matricine.
Figure 5
Figure 5
Effect of matricine on apoptosis-related protein expression at indicated concentrations. The experiments were performed in triplicate.
Figure 6
Figure 6
Effect of matricine on the migration of capan-2 cells. The experiments were performed in triplicate and results are shown as mean ±SD (* P<0.05).
Figure 7
Figure 7
Effect of matricine on the invasion of capan-2 cells. The experiments were performed in triplicate and results are shown as mean ±SD (* P<0.05).
Figure 8
Figure 8
Effect of matricine on mTOR/PI3K/AKT signalling pathway at indicated concentrations of matricine. The experiments were performed in triplicate.
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