Galloflavin Relieves the Malignant Behavior of Colorectal Cancer Cells in the Inflammatory Tumor Microenvironment

Background: In this study, we mainly aimed to explore the correlation between galloflavin and NLRP3 and its effect on colorectal cancer.Methods: NLRP3 was overexpressed in SW480 cells; LPS + ATP was used to mimic the inflammatory microenvironment. Wound healing assay and Transwell assay were utilized to detect cell migration and invasion abilities; CCK-8 assay was performed to detect cell viability alterations; colony formation assay was conducted to detect colony formation ability; Western blot was used to detect the levels of NLRP3, ASC, C-Myc, and P21. SW480 cells were pretreated with high-dose and low-dose galloflavin, followed by observation of their effects on cell metastasis and invasion. NLRP3 was knocked out in SW480 to construct the SW480-NLRP3−/− cell line, followed by high-dose galloflavin treatment and subsequent observation of cell metastasis and invasion abilities. Small molecule–protein docking and pull-down assay were performed to confirm the targeting relationship between galloflavin and NLRP3. After constructing a tumor-bearing mice model, galloflavin was intragastrically administered, followed by detection of tumor growth, expression of NLRP3 and ASC by immunohistochemistry, and tumor histopathology by H&E staining.Results: After NLRP3 overexpression and LPS/ATP induction in SW480, the cell migration and invasion abilities were significantly enhanced, and cell viability was also enhanced. The activation of NLRP3 could promote the malignant behavior of colorectal cancer cells in the inflammatory microenvironment. Galloflavin treatment could significantly attenuate the malignant behavior of SW480 in the inflammatory microenvironment and inhibit the migration and invasion capabilities of SW480. The knockout of NLRP3 inhibited the effect of galloflavin, which did not significantly change the migration and invasion abilities. Molecular docking and pull-down assay revealed a targeted binding relationship between galloflavin and NLRP3 and that galloflavin is bound to NLRP3 not ASC protein. Moreover, galloflavin could inhibit tumor growth and decrease the expression of NLRP in tumor-bearing mice.Conclusion: In this study, we found that NLRP3 could promote the migration and invasion of colorectal cancer cells in the inflammatory microenvironment. Galloflavin could inhibit the malignant behavior of colorectal cancer cells by targeting NLRP3.

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Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

Molecular Cancer ◽

10.1186/s12943-021-01354-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Simona Mareike Lüttgenau ◽

Christin Emming ◽

Thomas Wagner ◽

Julia Harms ◽

Justine Guske ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Cancer Cell ◽

Scaffolding Protein ◽

Migration And Invasion ◽

Tight Junction Formation ◽

Cell Metastasis ◽

Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

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Quercetin inhibits the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990

10.21203/rs.3.rs-1019635/v1 ◽

2021 ◽

Author(s):

Bin Chen ◽

Haijuan Xiao ◽

Linguangjin Wu ◽

Ting Wang ◽

Shuyun Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Luciferase Assay ◽

Migration And Invasion ◽

Colony Formation Assay ◽

Transwell Assay ◽

Protein Levels ◽

Colorectal Cancer Cells ◽

New Strategies ◽

Malignant Behavior

Abstract Background This study was intended to investigate the function of Quercetin in chemoresistant colorectal cancer (CRC) cells. In addition, this research aimed to explore the mechanism by which Quercetin regulates the malignant behavior of CRC cells. Methods To induce THP-1 cells into M2 tumor-associated macrophages (M2-TAMs), THP-1 cells were stimulated by PMA and IL-4. MDC staining was used to investigate the autophagy in M2-TAMs. Meanwhile, cell proliferation was tested by colony formation assay. In addition, wound healing and transwell assay were performed to detect the cell migration and invasion, respectively. Dual luciferase assay was used to investigate the correlation between hsa_circ_0006990 and miR-132-3p/miR-532-3p. Furthermore, mRNA and protein levels were detected by RT-qPCR and western blot, respectively. Results Quercetin suppressed autophagy of M2-TAMs. In addition, M2-TAMs significantly inhibited the apoptosis and promoted the proliferation of CRC cells, while this phenomenon was reversed by Quercetin. Meanwhile, the expression of hsa_circ_0006990 in CRC cells was decreased by M2-TAMs, while Quercetin reversed this phenomenon. Furthermore, overexpression of hsa_circ_0006990 significantly reversed the anti-tumor effect of Quercetin on CRC. Conclusion Quercetin inhibited the tumorigenesis of colorectal cancer cells through downregulation of hsa_circ_0006990. Thus, our study might shed new lights on exploring the new strategies against CRC.

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Mechanism of Ampelopsin Inhibiting Proliferation, Remove and Incursion of Colorectal Cancer Through Regulating the Expression of LncRNA ZFPM2-AS1/miR-515-5p

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2406 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1029-1036

Author(s):

Sheng Yuan ◽

Dazhong Yu

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Inhibitory Effect ◽

Expression Level ◽

Migration And Invasion ◽

Control Group ◽

Proliferation Inhibition ◽

Inhibition Rate ◽

Colorectal Cancer Cells ◽

Sw480 Cells

The incidence rate, recurrence and metastasis rate and mortality of colorectal cancer (CRC) are high. Therefore, clinical has been looking for better treatment. Ampelopsin (AMP) has obvious inhibitory effect on some tumors. However, there is no report on the effect and mechanism of AMP on rectal cancer. To investigate the effect and mechanism of AMP on the proliferation, migration and invasion of colorectal cancer cells, at first, different concentrations of Ampelopsis japonica group (10μM, 25 μM, 50 μM), control group (without AMP), pcDNA group, pcDNA-ZFPM2-AS1 group, si-NC group, si-ZFPM2-AS1 group, miR-NC group, miR-515-5p group, AMP+pcDNA group, AMP + pcDNA-ZFPM2-AS1 group were set up. Then the expression levels of miR-515-5p and ZFPM2-AS1 were detected by QRT-PCR, protein expression was detected by Western blot, cell proliferation inhibition rate was detected by MTT method, cell invasion and migration were detected by Transwell and fluorescence activity was detected by double luciferase reporter gene assay. The results show that compared with the control group, the proliferation inhibition rate of SW480 cells in different concentrations of AMP increased and the number of migration and invasion decreased significantly. Moreover, the expression levels of CyclinD1, MMP-2 and MMP-9 were significantly lower than those in the control group, while the expression of p21 was significantly increased. The expression level of miR-515-5pin SW480 cells treated with AMP was significantly increased, while the expression level of ZFPM2-AS1 was significantly decreased. Inhibition of ZFPM2-AS1 expression or miR-515-5p overexpression could inhibit the proliferation, migration and invasion of SW480 cells and then ZFPM2-AS1 overexpression reversed the inhibitory effect of AMP on the proliferation, migration and invasion of SW480 cells. Therefore, AMP affects the proliferation, migration and invasion of colorectal cancer cells by regulating the expression of lncRNA ZFPM2-AS1/miR-515-5p, which provides a new target and new idea for the prevention and treatment of colorectal cancer.

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