Comparison of the synergistic anticancer activity of AlPcS4 photodynamic therapy in combination with different low‑dose chemotherapeutic agents on gastric cancer cells

Yiqi Jianpi Huaji Decoction (YJHD), a traditional Chinese medicinal formula composed of twelve ingredients, has recently been reported to have a good clinical curative effect. The purpose of the present study was to evaluate the effects of YJHD on SGC7901/VCR gastric cancer cells and to elucidate the possible mechanism of action. First, the effects of a low dose of YJHD in combination with chemotherapeutic agents on SGC7901/VCR cells were assessed using the CCK-8 assay and flow cytometry, and the effects of YJHD on genes and proteins involved in drug resistance (MDR1, MRP, TUBB3, STMN1, and TS) were evaluated. Furthermore, transfection of SGC7901/VCR cells with siRNAs targeting these genes inhibited their expression, and the efficacy of vincristine against the cells was dramatically improved in vitro when these genes were silenced. These results demonstrate that low-dose YJHD inhibited cell proliferation, induced apoptosis, reversed MDR, and increased sensitivity to chemotherapeutic agents in vitro by downregulating P-gp, MRP, TUBB3, and STMN1 expression. MDR can be reversed by siRNAs targeting genes involved in MDR, and this strategy for cancer treatment should be evaluated in future studies.

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The Effect of Docetaxel (Taxotere®) on Human Gastric Cancer Cells Exhibiting Low-Dose Radiation Hypersensitivity

Clinical medicine Oncology ◽

10.4137/cmo.s463 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S463

Author(s):

Elizabeth K. Balcer-Kubiczek ◽

Mona Attarpour ◽

Jian Z. Wang ◽

William F. Regine

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Time Course ◽

Low Dose ◽

Immunoblot Analysis ◽

Human Gastric Cancer ◽

Low Dose Radiation ◽

Gastric Cancer Cells ◽

Dose Radiation

Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G2/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G2 checkpoint arrest. First we tested whether HRS occurs in gastric cancer—derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G2 accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G2 checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G2 checkpoint arrest. We speculate that G2 checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction.

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The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model

OncoTargets and Therapy ◽

10.2147/ott.s159935 ◽

2018 ◽

Vol Volume 11 ◽

pp. 3047-3057 ◽

Cited By ~ 5

Author(s):

Jiuhuan Feng ◽

Shukui Qin

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Fluorescence Imaging ◽

Synergistic Effects ◽

Xenograft Model ◽

Chemotherapeutic Agents ◽

Gastric Cancer Cells ◽

Gastric Cancer Xenograft

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Exosomal Micro RNA-107 Reverses Chemotherapeutic Drug Resistance of Gastric Cancer Cells Through HMGA2/mTOR/P-gp Pathway

10.21203/rs.3.rs-540926/v1 ◽

2021 ◽

Author(s):

Lu Jiang ◽

Yan Zhang ◽

Linghui Guo ◽

Chaoyang Liu ◽

Weihong Ren

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Cancer Cells ◽

Chemotherapeutic Agents ◽

Luciferase Reporter Assay ◽

Luciferase Reporter ◽

Reporter Assay ◽

Gastric Cancer Cells ◽

Chemotherapy Drug ◽

Chemotherapy Drugs

Abstract Background: RNA cargo in exosomes，especially microRNAs (miRNAs), play an important role in the chemotherapy drug resistance of human cancers. However, the role and mechanism of exosomal miR-107 on multidrug resistance of gastric cancer cells was still not clear. In this study, we sought to explore whether exosomal miR-107 could reverse theresistance of gastric cancer cells to the chemotherapy drugs. Methods: We extracted exosomes from sensitive (SGC-7901, MGC-803) and resistant (SGC-7901/5-FU) gastric cancer cells by ultracentrifugation and the isolated exosomes were identified using transmission electron microscopy (TEM) and dynamic light scattering analysis (DLS). The expression of miR-107 and high mobility group A2 (HMGA2) were detected by real-time quantitative PCR (RT-qPCR). MTT assay was used to investigate the effect of exosomes on gastric cancer cells growth in vitro. The uptake of exosomes by recipient cells were observed using a fluorescence microscope. The predicted target relationship between miR-107 and HMGA2 was verified by gauss-luciferase reporter assay. The expression of HMGA2, p-mTOR/mTOR, P-gp and other exosomal indicated marker proteins were detected by western blot. Results: Our results indicated that the isolated exosomes were demostrated typically cup-like lipid bilayer membrans structure. SGC-7901/5-FU cells were cross-resistant to chemotherapy drug cisplatin (DDP), and the sensitive cells-secreted exosomes drastically reversed the resistance of the resistant gastric cells to the chemotherapeutic drugs,which was verificated by exosomal inhibitor GW4896. Mechanistically, the reversal effect were mainly mediated by exosome-secreted miR-107 through downregulating the expression of targert molecular HMGA2, and inhibiting HMGA2/mTOR/P-gp pathway, which were proofed by luciferase reporter assay and rescue assay. Conclusions: These findings demonstrated that exosome-transmitted miR-107 significantly enhanced the sensitivity of resistant gastric cancer cells to chemotherapeutic agents by mediating the HMGA2/mTOR/P-gp axis and appling exosomal miR-107 may be a novel target in gastric cancers treatment.

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