scholarly journals Combined treatment with PI3K inhibitor BKM120 and PARP inhibitor olaparib is effective in inhibiting the gastric cancer cells with ARID1A deficiency

2018 ◽  
Author(s):  
Lin Yang ◽  
Guanghai Yang ◽  
Yingjun Ding ◽  
Yu Huang ◽  
Shunfang Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Combined Treatment ◽  
Pi3k Inhibitor ◽  
Gastric Cancer Cells

scholarly journals Sodium Selenite Accentuates the Therapeutic Effect of Adriamycin Prodrug (PADM) against Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Shengquan Tan ◽  
Jiapeng Mo ◽  
Zixiong Zhang ◽  
Chuying Huang ◽  
Yi Zou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Sodium Selenite ◽  
Therapeutic Potential ◽  
Mitochondrial Fission ◽  
Combined Treatment ◽  
Mitochondrial Morphology ◽  
Gastric Cancer Cells ◽  
Antitumor Effects ◽  
And Migration

Selenium has remained a controversial character in cancer research. While its antitumor effects have been widely demonstrated, further evidence is required to establish it as a robust treatment regime. Sodium selenite (SS), an inorganic selenium, reportedly affected the proliferation and redifferentiation of gastric cancer cells, but whether it could act as a complement to conventional chemotherapeutic drugs for combination therapy is uncertain. Herein, SGC-7901 and MGC-803 gastric cancer cells were treated with PADM (Ac-Phe-Lys-PABC-ADM), a prodrug of doxorubicin/adriamycin (ADM), and the combined antitumor effects of the two drugs were evaluated. Characterization after treatment revealed that although PADM exhibited antitumor effects individually by inhibiting the proliferation and migration of gastric cancer cells and inducing apoptosis, the addition of SS significantly amplified these effects. Furthermore, gastric cancer cell apoptosis triggered by the combined treatment of SS and PADM may involve the participation of mitochondrial apoptosis, as evidenced by the changes in mitochondrial morphology and occurrence of mitochondrial fission. Collectively, SS could be a strong complementary drug that accentuates the therapeutic potential of PADM in gastric cancer treatment and management, and its significance could contribute to unique and innovative anticancer strategies.

scholarly journals Combination of Sodium Selenite and Doxorubicin Prodrug Ac-Phe-Lys-PABC-ADM Affects Gastric Cancer Cell Apoptosis in Xenografted Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Bo Wu ◽  
Jian Ge ◽  
Zixiong Zhang ◽  
Chuying Huang ◽  
Xiaodan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Sodium Selenite ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Tumor Xenograft ◽  
Mitochondrial Apoptosis ◽  
Gastric Cancer Cells ◽  
Apoptosis Pathway

The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.

scholarly journals NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations

2011 ◽  
Vol 40 (4) ◽  
pp. 1259-1266 ◽  
Author(s):  
EUNJU PARK ◽  
JINAH PARK ◽  
SAE-WON HAN ◽  
SEOCK-AH IM ◽  
TAE-YOU KIM ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Pi3k Inhibitor ◽  
Human Gastric Cancer ◽  
Gastric Cancer Cells ◽  
Kras Mutations

scholarly journals Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Haiyong Zhang ◽  
Jing Wu ◽  
Jinqiu Yuan ◽  
Huafu Li ◽  
Yawei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Nude Mice ◽  
Combined Treatment ◽  
Thioredoxin Reductase ◽  
Tumor Growth Inhibition ◽  
Gastric Cancer Cells

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

scholarly journals Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 968
Author(s):  
Katarzyna Supruniuk ◽  
Robert Czarnomysy ◽  
Anna Muszyńska ◽  
Iwona Radziejewska
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Combined Treatment ◽  
T Antigen ◽  
Apoptotic Response ◽  
Gastric Cancer Cells ◽  
Bax Protein ◽  
Combined Action ◽  
Sialyl Tn

MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 μM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 μg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3, as well as pro- and cleaved caspase-3 protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to Bax protein and Bid expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards Akt and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy.

Abstract 1775: Growth inhibitory effect of PARP inhibitor olaparib in gastric cancer cells

2010 ◽  
Author(s):  
Seock-Ah Im ◽  
Ahrum Min ◽  
Hyung-Seok Hur ◽  
Young-Kwang Yoon ◽  
Sang Hyun Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Parp Inhibitor ◽  
Inhibitory Effect ◽  
Growth Inhibitory Effect ◽  
Gastric Cancer Cells ◽  
Growth Inhibitory

scholarly journals Enhanced Antitumor Effect of Trastuzumab and Duligotuzumab or Ipatasertib Combination in HER-2 Positive Gastric Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2339
Author(s):  
Maria Maddalena Laterza ◽  
Vincenza Ciaramella ◽  
Bianca Arianna Facchini ◽  
Elisena Franzese ◽  
Carmela Liguori ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Antitumor Effect ◽  
Combined Treatment ◽  
Human Gastric Cancer ◽  
Synergistic Activity ◽  
Her2 Positive ◽  
Gastric Cancer Cells

The anti-HER2 monoclonal antibody trastuzumab is a key drug for the treatment of HER2-positive gastric cancer (GC); however, its activity is often limited by the onset of resistance and mechanisms of resistance are still poorly understood. Several targeted agents showed synergistic activity by concomitant use with trastuzumab in vitro and are under clinical investigation. The aim of this study was to assess the antitumor activity of duligotuzumab, an anti HER3/EGFR antibody or ipatasertib, an AKT inhibitor, combined with trastuzumab in a panel of HER2-positive human gastric cancer cells (GCC), and the efficacy of such combinations in HER2-resistant cells. We have assessed the efficacy of duligotuzumab or ipatasertib and trastuzumab in combination, analyzing proliferation, migration and apoptosis and downstream intracellular signaling in vitro on human HER2-positive GCC (NCI-N87, OE33, OE19) and in negative HER2 GCC (MKN28). We observed a reduction of proliferation, migration and apoptotic rate in HER2-positive OE33, OE19 and N87 cell lines with the combination of duligotuzumab or ipatasertib plus trastuzumab. In particular, in OE33 and OE19 cell lines, the same combined treatment inhibited the activation of proteins downstream of HER2, HER3, AKT and MAPK pathways. Targeting both HER2 and HER3, or HER2 and AKT, results in an improved antitumor effect on HER2-positive GCC.

Toxicity against gastric cancer cells by combined treatment with 5-fluorouracil and mitomycin c: implication in oxidative stress

2009 ◽  
Vol 66 (3) ◽  
pp. 517-526 ◽  
Author(s):  
Toshiyuki Matsunaga ◽  
Yoshitaka Tsuji ◽  
Kairyu Kaai ◽  
Saki Kohno ◽  
Renzo Hirayama ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Cancer Cells ◽  
Mitomycin C ◽  
Combined Treatment ◽  
Gastric Cancer Cells
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