S-Adenosylmethionine enhances the inhibitory effect of gemcitabine against pancreatic cancer cells via suppression of the EGFR/AKT pathways

Author(s):  
Yan Liu ◽  
Linxun Liu ◽  
Yang Zhang ◽  
Lei Qin
2021 ◽  
Vol 13 (9) ◽  
pp. 1716-1723
Author(s):  
Jie Li ◽  
Chao Xu ◽  
Yueyue Lu ◽  
Yan Zhang ◽  
Xiaoping Tan

Nanoparticles are known to have recognition ability for targeted delivery, and are thus widely used in the treatments of diseases. Mesoporous nano-titanium dioxide (TiO2) nanoparticles have characteristics of nanomaterials and their porous structure with high surface area strengthens their drug-loading capacity and targeting ability. This study aimed to investigate the effect of mesoporous nano-TiO2 on pancreatic cancer cells and STAT pathway activity. Initially, we prepared mesoporous TiO2 nanoparticles that were characterized. Pancreatic cancer cells were co-cultured with mesoporous nano-TiO2 nanoparticles at different concentrations (0.1 μg/mL, 0.5 μg/mL, 1 μg/mL, 5 μg/mL, and 10 μg/mL) or 10 μg/mL nano-TiO2 (positive control group) or cells cultured alone (blank group). Cell viability was determined at several specific time points (24 h, 48 h, and 72 h). Transwell assay and scratching assay were conducted to determine the number of migrated and invaded cells. STAT3 and JAK2 expressions were examined by RT-qPCR and Western blot analysis. The prepared mesoporous nano-TiO2 exhibited sharp diffraction peaks with enhanced intensity and diffraction rings. STAT pathway was activated in pancreas cancer cells, which had more fluorescent cells than normal cells. The presence of mesoporous nano-TiO2 nanoparticles suppressed cancer cell viability and their inhibition rate increased with increased of nano-TiO2 concentration. The concentration of 10 μg/mL exhibited greatest inhibitory effect and 10 μg/mL mesoporous nano-TiO2 thus was chosen for experimental group. The width of the scratch in the experimental group (19.97±0.82 mm) was higher than in the blank group and positive control group (P < 0.05); 10 μg/mL mesoporous nano-TiO2 significantly decreased the number of invaded cells (71.97±17.84) and number of cell clones (156.91±31.03) (P < 0.05). The expression levels of STAT3 (0.41±0.06 μg/μL) and JAK2 (0.39±0.04 ug/ul) were diminished by treatment with mesoporous nano-TiO2. Mesoporous nano-TiO2 inhibits pancreatic cancer cell growth and STAT expression, as its inhibitory effect depends on its concentration. These findings might provide a novel insight into nanoparticle-based treatment for pancreatic cancer.


Pancreas ◽  
1994 ◽  
Vol 9 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Kazuo Sato ◽  
Jin Ishizuka ◽  
Cary W. Cooper ◽  
Dai H. Chung ◽  
Takashi Tsuchiya ◽  
...  

2001 ◽  
Vol 120 (5) ◽  
pp. A341
Author(s):  
Shoichiro Tsuji ◽  
Toshihiko Masui ◽  
Jun Ida ◽  
Sanae Nakajima ◽  
Michiya Kawaguchi ◽  
...  

2021 ◽  
Vol 16 (4) ◽  
pp. 1934578X2110040
Author(s):  
Xiang Ren ◽  
Yuran Ma ◽  
Xiao Wang ◽  
Xuetao Xu ◽  
Panpan Wu ◽  
...  

Natural products are very promising adjuvants with a variety of biological activities. Nobiletin, a citrus polymethoxyflavone, has been shown to exert an anticancer effect in various cell lines. In this study, we investigated the effects of nobiletin on cell viability, sphere formation, migration and invasion of pancreatic cancer cells, and the underlying mechanisms. Our results demonstrate that nobiletin significantly inhibited PANC-1 cell migration and invasion, and these effects were associated with downregulation of MMP-2. We also found that nobiletin, in a low concentration, exhibited a strong inhibitory effect on sphere formation. The potential molecular mechanisms were related to significant downregulation of p-mTOR and p-STAT3. Furthermore, we found that nobiletin combined with gemcitabine synergistically inhibited PANC-1 cell viability and sphere formation. The underlying mechanisms of the synergistic inhibition on growth were associated with decreases in p-STAT3 expression. Overall, our results suggest that nobiletin may be a promising candidate for pancreatic cancer adjuvant treatment.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 315
Author(s):  
Weirui Zhang ◽  
Yuping Zhu ◽  
Haobing Yu ◽  
Xiaoyu Liu ◽  
Binghua Jiao ◽  
...  

Libertellenone H (LH), a marine-derived pimarane diterpenoid isolated from arctic fungus Eutypella sp. D-1, has shown effective cytotoxicity on a range of cancer cells. The present study is to explore the anticancer effect of LH on human pancreatic cancer cells and to investigate the intracellular molecular target and underlying mechanism. As shown, LH exhibited anticancer activity in human pancreatic cancer cells by promoting cell apoptosis. Mechanistic studies suggested that LH-induced reactive oxygen species (ROS) accumulation was responsible for apoptosis as antioxidant N-acetylcysteine (NAC) and antioxidant enzyme superoxide dismutase (SOD) antagonized the inhibitory effect of LH. Zymologic testing demonstrated that LH inhibited Trx system but had little effect on the glutathione reductase and glutaredoxin. Mass spectrometry (MS) analysis revealed that the mechanism of action was based on the direct conjugation of LH to the Cys32/Cys35 residue of Trx1 and Sec498 of TrxR, leading to a decrease in the cellular level of glutathione (GSH) and activation of downstream ASK1/JNK signaling pathway. Taken together, our findings revealed LH was a marine derived inhibitor of Trx system and an anticancer candidate.


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