scholarly journals Activation of CXCL12/CXCR4 renders colorectal cancer cells less sensitive to radiotherapy via up-regulating the expression of survivin

2016 ◽  
Vol 242 (4) ◽  
pp. 429-435 ◽  
Author(s):  
Dawei Wang ◽  
Chengbin Jiao ◽  
Yanli Zhu ◽  
Deshen Liang ◽  
Ming Zao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Underlying Mechanism ◽  
Caspase 9 ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis ◽  
Common Malignancy ◽  
Cxcr4 Axis

Colorectal cancer is the most common malignancy of the gastrointestinal tract. Surgical treatment combined with radiotherapy is the main treatment course for colorectal cancer; nevertheless, radio-resistance is commonly encountered during the treatment course and seriously influences the therapeutic efficacy. We tested the hypothesis that the CXCL12/CXCR4 axis is closely related to radiotherapy sensitivity in colorectal cancer cells. Here, we found that the decrease in cell viability and the increase in cell death induced by radiotherapy were attenuated by CXCL12 treatment, and the inhibition of CXCR4 promoted colorectal cancer cells to be more sensitive to radiotherapy. We also examined the critical roles of CXCL12/CXCR4 in cell survival and found that radiotherapy induced Bax expression and facilitated the activity of caspase-3 and caspase-9, which were reversed by CXCL12 treatment. Cell apoptosis was enhanced by the inhibition of CXCR4 under radiotherapy conditions. Furthermore, treatment with CXCL12 resulted in an increased expression of survivin, and the inhibitory roles of CXCL12 in radiotherapy-induced apoptosis were mitigated by survivin knockdown. These results indicate that CXCL12/CXCR4 protects colorectal cancer cells against radiotherapy via survivin, implying an important underlying mechanism of resistance to radiotherapy during colorectal cancer therapy.

scholarly journals Anlotinib Overcomes Multiple Drug Resistant Colorectal Cancer Cells via Inactivating PI3K/AKT Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Weilan Lan ◽  
Jinyan Zhao ◽  
Wujin Chen ◽  
Haixia Shang ◽  
Jun Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Inhibition Of Proliferation ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

Background: Anlotinib is a multi-target tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the mechanisms of how anlotinib mediates drug-resistance of colorectal cancer have not been fully described. Particularly the potential mechanisms regarding to the inhibition of proliferation and induction of apoptosis remain unknown. Objective: In this study, we intended to study the effect and related-mechanism of the proliferation, migration, invasion and induced apoptosis of anlotinib overcoming multidrug resistant colorectal cancer cells through in vitro experiments. Methods: Cell viability was determined by MTT assays and the resistant index was calculated. Colony formation and PI/RNase Staining were used for testing the proliferation of resistant cells. DAPI staining and Annexin V-FITC/PI staining were used to detect cell apoptosis. Migration and invasion were examined by transwell. Protein expression and activation of PI3K/AKT pathway were detected by western blot. LY294002 was used to verify whether anlotinib overcomes the drug-resistance of CRC cells by inactivating the PI3K/AKT pathway. Results: The results showed that the HCT-8/5-FU cells were resistant to multiple chemotherapy drugs (5-FU, ADM and DDP). Anlotinib significantly inhibited the cell viability, proliferation, migration, invasion and induced the cell apoptosis. Moreover, anlotinib downregulated the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, MMP-9, vimentin and N-cadherin, but up-regulated cleaved-caspase-3, Bax and E-cadherin and blocked the activity of the PI3K/AKT in HCT-8/5-FU cells. We found anlotinib and LY294002 overcame the drug resistance of HCT-8/5-FU cells by reducing the expression of PI3K/p-AKT. Conclusions: Anlotinib inhibited the proliferation, migration, invasion and induced apoptosis of HCT-8/5-FU cells, and the mechanisms may be that anlotinib conquered multidrug resistance of colorectal cancer cells via inactivating of PI3K/AKT pathway.

Coptidis rhizoma Induces Apoptosis in Human Colorectal Cancer Cells SNU-C4

2004 ◽  
Vol 32 (06) ◽  
pp. 873-882 ◽  
Author(s):  
Youn Jung Kim ◽  
Soon Ah Kang ◽  
Mee Suk Hong ◽  
Hae Jeong Park ◽  
Mi-Ja Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
Coptidis Rhizoma ◽  
Human Colorectal Cancer Cells

Coptidis rhizoma has been used as traditional herb medicine in gastrointestinal disorders in the Eastern Asia. We investigated whether the anticancer effects of the C. rhizoma induced apoptosis on human colorectal cancer cells SNU-C4. The cytotoxic effect of C. rhizoma was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To determine apoptotic cell death, 4,6-diamidino-2-phenylindole (DAPI) staining, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 enzyme assay were performed. In this study, C. rhizoma treatment (100 μg/ml) revealed typical morphological apoptotic features. Additionally, C. rhizoma treatment (100 μg/ml) increased levels of BAX and CASPASE-3, and decreased levels of BCL-2. Caspase-3 enzyme activity by treatment of C. rhizoma (100 μg/ml) also significantly increased compared to the control (p<0.05). These data indicate that C. rhizoma caused cell death by apoptosis through caspase pathways on human colorectal cancer cells SNU-C4.

scholarly journals Knockdown of Mir-135b Sensitizes Colorectal Cancer Cells to Oxaliplatin-Induced Apoptosis Through Increase of FOXO1

2018 ◽  
Vol 48 (4) ◽  
pp. 1628-1637 ◽  
Author(s):  
Yan Qin ◽  
Longhai Li ◽  
Fang Wang ◽  
Xinyi Zhou ◽  
Yankui Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Pcr Analysis ◽  
Aberrant Expression ◽  
Colorectal Cancer Cells ◽  
Novel Strategy ◽  
Induced Apoptosis

Background/Aims: Aberrant expression of microRNAs (miRNAs) is found to be responsible for tumorigenesis, cancer development and chemoresistance. Although oxaliplatin is an effective chemotherapeutic drug for treatment of colorectal cancer (CRC), CRC cells can develop some mechanisms to evade oxaliplatin-induced cell death. It is urgent to explore the novel strategies to increase the chemosensitivity of CRC cells. Methods: QRT-PCR analysis was performed to detect the expression of miR-135b in CRC patients’ serum and CRC cell lines. MTT assays were used to evaluate the effect of anti-miR-135b on oxaliplatin-induced cell death in CRC cell lines. Western blot, flow cytometry and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of anti-miR-135b-promoted apoptosis in oxaliplatin-treated CRC cells. Results: Significant upregulation of miR-135b was observed in CRC cell lines and CRC patients’ serum. Knockdown of miR-135b was found to sensitize colorectal cancer cells to oxaliplatin-induced cytotoxicity. Mechanically, knockdown of miR-135b increased the expression level of FOXO1 in CRC. As the downstream, the increased FOXO1 induced by anti-miR-135b promoted the expression of Bim and Noxa. Since Bim and Noxa act as key pro-apoptotic proteins in mitochondrial apoptosis, anti-miR-135b was able to enhance the oxaliplatin-induced apoptosis dependent on the anti-miR-135b/FOXO1 axis. Conclusions: Anti-miR-135b enhanced the anti-tumor effect of oxaliplatin on CRC. Combination with miR-135b antisense nucleotides may represent a novel strategy to sensitize CRC to oxaliplatin-based treatment.

scholarly journals The essential role of TAp73 in bortezomib-induced apoptosis in p53-deficient colorectal cancer cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yasamin Dabiri ◽  
Sara Kalman ◽  
Clara-Marie Gürth ◽  
Jee Young Kim ◽  
Viola Mayer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Essential Role ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages

2001 ◽  
Vol 280 (1) ◽  
pp. L10-L17 ◽  
Author(s):  
Han-Ming Shen ◽  
Zhuo Zhang ◽  
Qi-Feng Zhang ◽  
Choon-Nam Ong
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Alveolar Macrophages ◽  
Caspase 3 ◽  
Reactive Oxygen ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Caspase Activation ◽  
Caspase 9 ◽  
Induced Apoptosis

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.

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