scholarly journals Inhibitory Effect of Oat Bran Ethanol Extract on Survival and Gemcitabine Resistance of Pancreatic Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3829 ◽  
Author(s):  
Myoungjae Kim ◽  
Jeong-Geon Mun ◽  
Hyun Jin Lee ◽  
So-Ri Son ◽  
Mi-Ja Lee ◽  
...  

Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14141-14141
Author(s):  
H. Cheng ◽  
J. G. Yan ◽  
Y. Jiang

14141 Background: Human pancreatic cancer is a devastating disease. Standard therapy, gemcitabine, is not able to alter the natural history of the disease. Targeting intracellular signaling molecules has proven to be a powerful approach in cancer therapy. Protein kinase C (PKC) family has been implicated in many human cancers including pancreatic cancer. Methods: In this pre-clinical study, we evaluated the effect of a novel small molecule inhibitor, enzastaurin, for PKCβ on human pancreatic cancer cells. We utilized MTT assay to assess cell proliferation and viability. To evaluate cell transforming activity, soft agar colony forming assay was used. Results: We showed that with addition of 20μM enzastaurin into the culture, the proliferative growth of two pancreatic cancer cell lines, Panc1 and L3.6p1, was significantly attenuated, as measured by the MTT assay. In addition, the combination of enzastaurin and a low dose of gemcitabine (25 nM) resulted in a synergistic cytotoxic effect in L3.6p1 cells. Further, the in vitro tumorogenicity assay demonstrated that the L3.6p1 cells treated with enzastaurin (20μM) formed much smaller colonies than the control parental cells in 0.4% soft-agar. Consistent with the in vitro cell proliferation results, the combination of enzastaurin and the low concentration of gemcitabine (25nM) further reduced the numbers and sizes of colonies in the soft-agar. Conclusions: Collectively, our data indicate that enzastaurin can effectively suppress the proliferation and in vitro transforming activity of the pancreatic cells, and more effectively when applied in combination with the low dose of gemcitabine. No significant financial relationships to disclose.


Nanoscale ◽  
2017 ◽  
Vol 9 (32) ◽  
pp. 11739-11753 ◽  
Author(s):  
Baoyue Ding ◽  
Md Arif Wahid ◽  
Zhijun Wang ◽  
Chen Xie ◽  
Arvind Thakkar ◽  
...  

Novel combination of triptolide and celastrol loaded silk fibroin nanoparticles show synergistic anti-pancreatic cancer effect in vitro.


2012 ◽  
Vol 98 (6) ◽  
pp. 804-811 ◽  
Author(s):  
Zhiping Zhang ◽  
Zhou Wang ◽  
Xiangyan Liu ◽  
Jie Wang ◽  
Feng Li ◽  
...  

Aims and background To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. Methods and study design A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. Results The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo. Conclusions dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.


2021 ◽  
Author(s):  
Congfei Wang ◽  
Mingjuan Fu ◽  
Heguang Huang ◽  
Jieming Xie

Abstract Objective To investigate the effects of cucurmosin (CUS) on proliferation and drugs resistance in gemcitabine (GEM) human pancreatic cancer cell PANC-1RG7. Methods The ultrastructural changes of PANC-1RG7 cells after CUS intervention were observed by transmission electron microscope. Flow Cytometer (FCM) was used to detect the effect of CUS on the growth cycle of PANC-1RG7 cells. We used colony formation experiment, Sulforhodamine B assays and subcutaneous implantation tumor model to observe the proliferation inhibition and reversal drug-resistance reversion of CUS on PANC-1RG7 in vitro and in vivo. Western blot was used to observe the expressions of RRM1, RRM2, PI3K, Akt, mTOR and other proteins related to apoptosis after CUS intervention. Results After CUS intervention, PANC-1RG7 cells were obviously apoptotic with large number of vacuoles and apoptotic bodies. Compared with parental cell PANC-1, GEM-resistant cell PANC-1 was more sensitive to CUS. The combination of GEM and CUS at different concentrations showed synergistic effect. At the concentration of CUS with the inhibition rate of 10%, the reversal multiples and the reversal efficiency were 1.78±0.65 and 50.13±16.87%, respectively. Subcutaneous implantation tumor model confirmed the proliferation inhibitory effect of CUS in vitro. Western blot confirmed that CUS down-regulated the expressions of RRM1, RRM2, PI3K, Akt and mTOR. Conclusion CUS can significantly inhibit PANC-1RG7 cell proliferation in vivo and in vitro, and can reverse cell GEM-resistance.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 331-331
Author(s):  
Doron Feinsilber ◽  
Cliff Whatcott ◽  
Marc Ryan Matrana ◽  
John T. Cole ◽  
Ruben Munoz ◽  
...  

331 Background: Statins have been shown to possess antiproliferative activity in-vitro. Synergism with multiple drug combinations has been of great interest in pancreatic cancer. We examined 2 in-vitro cell models for synergism using a combination of fluvastatin and nab-paclitaxel. Methods: Pancreatic cancer cell lines Mia-Paca-2 (MP2) and Su86 were cultivated and seeded to 25,000 cells/mL and subsequently grown in 96 well plates for 24 hours. The cells were then treated with a fixed concentration of fluvastatin in 9 rows, 8 receiving serial 1:2 dilutions 16 times in triplicate of nab-paclitaxel, 1 fluvastatin only row, and 1 untreated. Upon dosing cells were incubated for 72 hrs. Cellular proliferation was determined by sulforhodamine B proliferation assays and read at 570 nm. A nab-paclitaxel only assay was done as well for comparison. Results: The lowest inhibitory concentration of fluvastatin in combination with nab-paclitaxel was between 500-600 micro mole (mm). Fluvastatin alone at these concentrations attenuated cellular proliferation. Synergism was seen on IC50 curves that are available. Anti-proliferative effects were reduced by 1:256 dilution. Conclusions: Preliminary studies show fluvastatin has an in-vitro anti proliferative effect on Su86 and MP2 cells and synergism in combination with nab-paclitaxel. Fluvastatin is more cytotoxic in Su86 than MP2. Future experimental design will focus on in-vivo models.


2010 ◽  
Vol 999 (999) ◽  
pp. 1-11
Author(s):  
P. Ulivi ◽  
C. Arienti ◽  
W. Zoli ◽  
M. Scarsella ◽  
S. Carloni ◽  
...  

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