A molecular basis for the synergy between 17‑allylamino‑17‑demethoxy geldanamycin with Capecitabine and Irinotecan in human colorectal cancer cells through VEFG and MMP-9 gene expression

Zeynali-Moghaddam, Shima; Mohammadian, Mahshid; Kheradmand, Fatemeh; Azarbayjani, Anahita Fathi; Rasmi, Yousef; Esna-Ashari, Omid; Malekinejad, Hassan

doi:10.1016/j.gene.2018.10.016

Cited by 27 publications

(22 citation statements)

References 47 publications

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“…As colorectal tumors with good response to chemotherapy with 5-FU had low DPD gene expression levels, 31 the higher cytotoxicity levels in our double treated groups might be a sign of involvement of some other pathways (except DPD pathway) like apoptosis or oxidative stress on the effect of the combination of chemotherapeutic agents as compared to single group drugs. 14-16…”

Section: Resultsmentioning

confidence: 99%

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Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

et al. 2019

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Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.

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Section: Resultsmentioning

confidence: 99%

“…7-17 Cytotoxic effects of 17-AAG in combination with oxaliplatin, 5-fluorouracil (5-FU) and capecitabine, were reported in previous studies. 14-16 In our previous study, 17-AAG revealed synergistic interaction with oxaliplatin and capecitabine in double combinations at the concentration of 0.5× IC50 in HCT-116 and HT-29 cell lines. 17…”

Section: Introductionmentioning

confidence: 92%

Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

et al. 2019

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“…Moreover, angiogenesis is also closely related to tumor growth, invasion and metastasis. Shima et al have proved that matrix metalloproteinase, such as MMP-9, is directly related to angiogenesis and metastasis 31. So next, we studied the expression of CD31 (vascular endothelial cell marker) in tumor tissues.…”

Section: Resultsmentioning

confidence: 96%

An in situ microenvironmental nano-regulator to inhibit the proliferation and metastasis of 4T1 tumor

et al. 2019

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Tumor microenvironment, such as hypoxia and presence of immune cells, plays a critical role in cancer initiation, growth as well as progression, and seriously affects antitumor effect. Accordingly, we constructed a kind of multifunctional nanoparticles (NPs) with macrophage transformation and oxygen (O 2 ) generation characteristics, to regulate the tumor microenvironment. Methods: In this study, we synthesized mesoporous Prussian blue (MPB) NPs with low molecular weight hyaluronic acid (LMWHA) surface modification (LMWHA-MPB), and discovered that LMWHA-MPB could be used as an in situ macrophages converter and O 2 generator. Results: In vitro results showed after uptake by M2 macrophages, LMWHA-MPB displayed the potential in remodeling tumor-associated macrophages (TAMs) phenotype (pro-tumor M2→anti-tumor M1), and anti-metastatic effect on 4T1 cells. Furthermore, in vivo visualized near-infrared (NIR) imaging data proved IR783 labeled LMWHA-MPB NPs could selectively accumulate in tumor sites. Then plenty of O 2 generated to alleviate tumor hypoxia via catalytic decomposition of endogenous hydrogen peroxide (H 2 O 2 ). Based on these outstanding characteristics, LMWHA-MPB NPs were adopted as multifunctional nanocarriers to load sonosensitizer hematoporphyrin monomethyl ether (HMME) for O 2 self-provided sonodynamic therapy (SDT). In vivo anti-tumor results showed LMWHA-MPB/HMME could effectively inhibit the proliferation and metastasis of 4T1 tumors by improving tumor microenvironment. Conclusion: The multifunctional NPs can be used as in situ microenvironmental nano-regulators to inhibit the proliferation and metastasis of 4T1 tumor.

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“…8 A, C and D, in comparison with Control and Control+L (808+635 nm laser) groups, the expression of MMP-9 and Ki67 significantly decreased in BP and HA-BP groups, and almost no the expression of MMP-9 and Ki67 was observed in HA-BP+L (808+635 nm laser) group, implying the reduced metastasis and proliferation activities of tumor cells caused by BP and HA-BP nanoparticles. Besides, matrix metalloproteinase is proved to be directly involved in angiogenesis and invasion [ 58 ]. So we further explored the expression of CD31, a marker of vascular endothelial and indicator of angiogenesis at the tumor sites, the results were shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

A targeting black phosphorus nanoparticle based immune cells nano-regulator for photodynamic/photothermal and photo-immunotherapy

Zhang¹,

Tang²,

Li³

et al. 2021

Bioactive Materials

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Photo-immunotherapy is a novel therapeutic approach against malignant tumors with minimal invasiveness. Herein, a targeting multifunctional black phosphorus (BP) nanoparticle, modified by PEGylated hyaluronic acid (HA), was designed for photothermal/photodynamic/photo-immunotherapy. In vitro and in vivo assays indicated that HA-BP nanoparticles possess excellent biocompatibility, stability, and sufficient therapeutic efficacy in the combined therapy of photothermal therapy (PTT) and photodynamic therapy (PDT) for cancer therapy. Moreover, the results of in vitro showed that HA-BP down-regulated the expression of CD206 (M2 macrophage marker) by 42.3% and up-regulated the ratio of CD86（M1 macrophage marker）by 59.6%, indicating that HA-BP nanoparticles have functions in remodeling tumor associated macrophages (TAMs) phenotype (from pro-tumor M2 TAMs to anti-tumor M1 macrophages). Fluorescence (FL) and photoacoustic (PA) multimodal imaging confirmed the selective accumulation of HA-BP in tumor site via both CD44 + mediated active targeting and passive EPR effect. In vitro and in vivo studies suggested that the combined therapy of PDT, PTT and immunotherapy using HA-BP could not only significantly inhibit original tumor but also induce immunogenic cell death (ICD) and release Damage-associated molecular patterns (DAMPs), which could induce maturation of dendritic cells (DCs) and activate effector cells that robustly evoke the antitumor immune responses for cancer treatment. This study expands the biomedical application of BP nanoparticles and displays the potential of modified BP as a multifunctional therapeutic platform for the future cancer therapy.

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A molecular basis for the synergy between 17‑allylamino‑17‑demethoxy geldanamycin with Capecitabine and Irinotecan in human colorectal cancer cells through VEFG and MMP-9 gene expression

Cited by 27 publications

References 47 publications

Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

Dihydropyrimidine Dehydrogenase Levels in Colorectal Cancer Cells Treated with a Combination of Heat Shock Protein 90 Inhibitor and Oxaliplatin or Capecitabine

An in situ microenvironmental nano-regulator to inhibit the proliferation and metastasis of 4T1 tumor

A targeting black phosphorus nanoparticle based immune cells nano-regulator for photodynamic/photothermal and photo-immunotherapy

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