scholarly journals Selenium Induces Pancreatic Cancer Cell Death Alone and in Combination with Gemcitabine

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 149
Author(s):  
David J. Wooten ◽  
Indu Sinha ◽  
Raghu Sinha
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Single Agent ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Cancer Cell Death ◽  
Pancreatic Cancer Cells

Survival rate for pancreatic cancer remains poor and newer treatments are urgently required. Selenium, an essential trace element, offers protection against several cancer types and has not been explored much against pancreatic cancer specifically in combination with known chemotherapeutic agents. The present study was designed to investigate selenium and Gemcitabine at varying doses alone and in combination in established pancreatic cancer cell lines growing in 2D as well as 3D platforms. Comparison of multi-dimensional synergy of combinations’ (MuSyc) model and highest single agent (HSA) model provided quantitative insights into how much better the combination performed than either compound tested alone in a 2D versus 3D growth of pancreatic cancer cell lines. The outcomes of the study further showed promise in combining selenium and Gemcitabine when evaluated for apoptosis, proliferation, and ENT1 protein expression, specifically in BxPC-3 pancreatic cancer cells in vitro.

Identification and characterization of CCK-B/gastrin receptors in human pancreatic cancer cell lines

1994 ◽  
Vol 266 (1) ◽  
pp. R277-R283 ◽  
Author(s):  
J. P. Smith ◽  
G. Liu ◽  
V. Soundararajan ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cells

The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth of human pancreatic cancer in a receptor-mediated fashion. The purpose of this study was to characterize the receptor responsible for the trophic effects of CCK in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer cells grown in vitro, the binding characteristics and optimal conditions of radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718) were examined. Specific and saturable binding was detected with [3H]L-365,260, and Scatchard analysis revealed that the data were consistent for a single site of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on protein concentration, time, temperature, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and postconfluent cultures, respectively. Subcellular fractionation studies revealed that binding was in the membrane fraction. Competition experiments indicated that L-365,260 and gastrin were more effective at displacing the radiolabeled L-365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L-364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic cancer cell lines in vitro and tumor tissue from xenografts in nude mice also revealed specific and saturable binding. These results provide the first identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and tumors and explain the effects of CCK on the growth of this malignancy.

scholarly journals Evaluation of the In Vitro Cytotoxic Activity of Caffeic Acid Derivatives and Liposomal Formulation against Pancreatic Cancer Cell Lines

Materials ◽  
2020 ◽  
Vol 13 (24) ◽  
pp. 5813
Author(s):  
Magdalena Zaremba-Czogalla ◽  
Anna Jaromin ◽  
Katarzyna Sidoryk ◽  
Agnieszka Zagórska ◽  
Marcin Cybulski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cytotoxic Activity ◽  
Caffeic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Liposomal Formulation ◽  
Caffeic Acid Derivatives

Pancreatic cancer belongs to the most aggressive group of cancers, with very poor prognosis. Therefore, there is an important need to find more potent drugs that could deliver an improved therapeutic approach. In the current study we searched for selective and effective caffeic acid derivatives. For this purpose, we analyzed twelve compounds and evaluated their in vitro cytotoxic activity against two human pancreatic cancer cell lines, along with a control, normal fibroblast cell line, by the classic MTT assay. Six out of twelve tested caffeic acid derivatives showed a desirable effect. To improve the therapeutic efficacy of such active compounds, we developed a formulation where caffeic acid derivative (7) was encapsulated into liposomes composed of soybean phosphatidylcholine and DSPE-PEG2000. Subsequently, we analyzed the properties of this formulation in terms of basic physical parameters (such as size, zeta potential, stability at 4 °C and morphology), hemolytic and cytotoxic activity and cellular uptake. Overall, the liposomal formulation was found to be stable, non-hemolytic and had activity against pancreatic cancer cells (IC50 19.44 µM and 24.3 µM, towards AsPC1 and BxPC3 cells, respectively) with less toxicity against normal fibroblasts. This could represent a promising alternative to currently available treatment options.

Inhibition of cMET in an experimental model of pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 185-185
Author(s):  
Sven A. Lang ◽  
Franziska Brandes ◽  
Edward K. Geissler
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Oncogenic Signaling

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P<0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P<0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.

scholarly journals In vitro evaluation of photon and raster-scanned carbon ion radiotherapy in combination with gemcitabine in pancreatic cancer cell lines

2013 ◽  
Vol 54 (suppl 1) ◽  
pp. i113-i119 ◽  
Author(s):  
R. A. El Shafie ◽  
D. Habermehl ◽  
S. Rieken ◽  
A. Mairani ◽  
L. Orschiedt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Carbon Ion Radiotherapy ◽  
In Vitro Evaluation ◽  
Carbon Ion

Mir-320b inhibits pancreatic cancer cell proliferation by targeting FOXM1

2020 ◽  
Vol 21 ◽  
Author(s):  
Zhou Jingyang ◽  
Che Jinhui ◽  
Xu Lu ◽  
Yang Weizhong ◽  
Li Yunjiu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Negative Relationship ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Brdu Incorporation ◽  
Pancreatic Cancer Cells

Backround: Pancreatic ductal adenocarcinoma (PDAC) is the most common and deadly cancer. Surgical resection is the only possible cure for pancreatic cancer but often has a poor prognosis, and the role of adjuvant therapy is urgently explored. Methods: MicroRNAs (miRNAs) play very important role in tumorigenesis by regulating the target genes. In this study, we identified miR-320b lower-expressed in human pancreatic cancer tissues but relatively higher-expressed in the adjacent nontumor tissues. Results: Consistently，the expression of miR-320b in different pancreatic cancer cell lines was significantly lower than the normal pancreatic cells. In order to identify the effects of miR-320b on cell growth, we overexpressed miR-320b in PANC-1 and FG pancreatic cancer cell lines, CCK8 and BrdU incorporation assay results showed that miR-320b inhibited cell proliferation. Discussion: We next predicted miR-20b targeted FOXM1（Forkhead box protein M1）and identified the negative relationship between miR-320b and FOXM1.We also demonstrated that elevated miR-320b expression inhibited tumor growth in vivo. Conclusion: All of these results showed that miR-320b suppressed pancreatic cancer cells proliferation by targeting FOXM1, which might provide a new diagnostic marker for pancreatic cancer.

Enhanced antitumor effect via combination of triptolide with 5-fluorouracil in pancreatic cancer cell lines.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 352-352 ◽  
Author(s):  
Wei Wang
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Effect ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Advanced Pancreatic Cancer ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Mechanism Study ◽  
Pancreatic Cancer Cells

352 Background: Pancreatic cancer is one of the most aggressive types of cancer, and lack of effective treatment results in a very low 6-month survival rate. This study aims to explore the enhancement of therapeutic effect on human pancreatic cancer cell lines (AsPC-1, MiaPaCa-2 and PANC-1) via combination of triptolide (TPL),derived from the herb Tripterygium wilfordii, and 5-fluorouracil (5-FU). Methods: Cell proliferation was measured by MTT, apoptotic cells were assessed by flow cytometry and western blot for cleaved caspase-8, 9, 3 and PARP. To explore the role of nuclear factor kappaB (NF-kB) activity in pancreatic cancer cell lines, AsPC-1/IkBaM and PANC-1/IkBaM cells (NF-kB activity of AsPC-1 and PANC-1 cells was silenced by IkB-a mutation) were treated with TPL plus 5-FU. NF-kB activity was determined by electrophoretic mobility shift assay. Results: TPL demonstrated toxicity on three pancreatic cancer cell lines with the IC50 of 25-40 nM. The combination of TPL (IC30 concentration) and 5-FU enhanced the cytotoxicity significantly compared to not only 5-FU alone but also Gemcitabine (the first line drug for advanced pancreatic cancer) alone. Combination index (CI) indicated the effect of TPL plus 5-FU was highly synergistic. Furthermore, pancreatic cancer cells treated with TPL plus 5-FU exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with TPL or 5-FU or Gemcitabine alone. In the mechanism study, AsPC-1/IkBaM and PANC-1/IkBaM cells showed more resistance to enhanced apoptosis induced by TPL plus 5-FU compared to wild-type cells. It indicated the enhanced effect of TPL was related with NF-kB activity. Conclusions: 1) TPL has a potent therapeutic effect on pancreatic cancer cell lines; 2) the combination of TPL with 5-FU enhances the therapeutic effect which is more powerful than Gemcitabine in vitro, low concentration of TPL showed high synergistic effect with 5-FU; 3) the inhibitory effect of TPL plus 5-FU on pancreatic cancer is mediated by the induction of apoptosis and TPL enhanced the apoptosis via inhibition of NF-kB activity.

The enhanced antitumor effect of combined triptolide and paclitaxel on pancreatic cancer cell lines.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 335-335
Author(s):  
Wei Wang ◽  
Wenjie Lin ◽  
Qingda Wang ◽  
Xin Zhuang ◽  
Jinbing Luo
Keyword(s):  
Pancreatic Cancer ◽  
Synergistic Effect ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Effect ◽  
Pancreatic Cancer Cell ◽  
Advanced Pancreatic Cancer ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

335 Background: Pancreatic cancer is a disease with dismal prognosis and its treatment options are limited. Recently albumin-bound paclitaxel (nab-paclitaxel) was approved by FDA for advanced pancreatic cancer patients. This study aims to explore the enhancement of therapeutic effect on human pancreatic cancer cell lines (AsPC-1 and PANC-1) via the combination of triptolide, derived from the herb Tripterygium wilfordii, and paclitaxel. Methods: Pancreatic cells were treated with paclitaxel or triptolide alone, and the combination of them. Cell proliferation was measured by sulforhodamine B (SRB). Apoptotic cells were assessed by flow cytometry and western blot for cleaved caspase-3, 8, 9 and PARP. To explore the role of nuclear factor kappaB (NF-kB) activity in pancreatic cancer cell lines, AsPC-1/IkBaM and PANC-1/IkBaM cells (NF-kB activity of cells was silenced by IkB-a mutation) were treated with triptolide plus paclitaxel and NF-kB activity were analyzed. Results: Triptolide demonstrated cytotoxicity on pancreatic cancer cell lines with the IC50 of 25-40nM. The combination of triptolide (IC30 concentration) and paclitaxel enhanced the cytotoxicity significantly . Combination index (CI) indicated that the effect of triptolide plus paclitaxel was synergistic. Furthermore, pancreatic cancer cells treated with triptolide plus paclitaxel exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with paclitaxel or gemcitabine alone. In the mechanism study, the combination of triptolide and paclitaxel did not demonstrate synergistic effect on AsPC-1/IkBaM and PANC-1/IkBaM cells. It indicated that the enhanced effect of triptolide plus paclitaxel was correlated with NF-kB activity. Conclusions: (1) the combination of triptolide and paclitaxel enhances the apoptosis in vitro, low concentration of triptolide showed synergistic effect with paclitaxel; (2) the antitumor effect of triptolide plus paclitaxel on pancreatic cancer is mediated by the induction of apoptosis and triptolide enhances paclitaxel-mediated apoptosis via suppression of NF-kB activity.

In vitro chemosensitivity of human pancreatic cancer cell lines

1996 ◽  
Vol 20 (3) ◽  
pp. 185-190 ◽  
Author(s):  
Yasunori Sawabe ◽  
Hisakazu Yamagishi ◽  
Nozomi Yamaguchi ◽  
Yoshiro Yamamura ◽  
Takahiro Oka
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
In Vitro Chemosensitivity

Effect of triptolide on gemcitabine-mediated apoptosis in pancreatic cancer cell lines.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22043-e22043
Author(s):  
Wei Wang ◽  
Wenjie Lin
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Pancreatic Cancer Cell ◽  
Chinese Herb ◽  
Annexin V ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells

e22043 Background: Pancreatic cancer is notorious for its resistance to anticancer drug. gemcitabine, the most effective anticancer drug currently available for palliative chemotherapy in pancreatic cancer patients, hardly achieves clinically satisfactory response rates. Therefore, it is urgent to develop novel agents that overcome drug resistance of pancreatic cancer. In this study, we demonstrated for the first time that triptolide, a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F, can enhance gemcitabine-mediated apoptosis in human pancreatic cancer cell lines (AsPC-1 and PANC-1). Methods: Pancreatic cells were treated with gemcitabine or triptolide alone, and combination of them, cell viability was measured by MTT, and apoptotic cells were assessed by flow cytometry for Annexin V/PI staining and western blot for cleaved caspase-3, 8, 9 and PARP. To explore the mechanism of enhancement of triptolide and gemcitabine, proteomic approach was used to screen the related apoptosis factors. Results: Triptolide demonstrated toxicity on pancreatic cancer cell lines with the IC50 of 25-40 nM. The combination of triptolide (IC30 concentration) and gemcitabine enhanced the cytotoxicity significantly compared to gemcitabine alone. Combination index (CI) indicated the effect of triptolide plus gemcitabine was synergistic. Furthermore, pancreatic cancer cells treated with triptolide plus gemcitabine exhibited increased apoptosis, as evidenced by stronger Annexin V/ PI staining, higher levels of pro-apoptotic proteins including cleaved caspases and activated PARP compared to cells treated with gemcitabine alone. In the mechanism study, vimentin, a mesenchymal marker, was screened out to be correlated with enhanced apoptosis induced by triptolide plus gemcitabine. Conclusions: 1) Triptolide has a potent therapeutic effect on pancreatic cancer cell lines; 2) the combination of triptolide with gemcitabine enhances the apoptosis in vitro, low concentration of TPL showed synergistic effect with gemcitabine; 3) The enhanced apoptosis induced by triptolide plus gemcitabine is correlated with vimentin expression inhibited by triptolide.

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