scholarly journals Overactivation of Akt Contributes to MEK Inhibitor Primary and Acquired Resistance in Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1866 ◽  
Author(s):  
Tsubaki ◽  
Takeda ◽  
Noguchi ◽  
Jinushi ◽  
Seki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Critical Role ◽  
Pik3ca Mutation ◽  
Acquired Resistance ◽  
Mek Inhibitor ◽  
Blue Dye ◽  
Colorectal Cancer Cells ◽  
Inhibitor Resistance ◽  
Ht 29

RAS and BRAF-mutated colorectal cancers are associated with resistance to chemotherapy and poor prognosis, highlighting the need for new therapeutic strategies. Although these cancers sometimes respond to mitogen activated protein kinase kinase (MEK) inhibitor treatment, they often acquire resistance via mechanisms, which are poorly understood. Here, we investigated the mechanism of MEK inhibitor resistance in primary- and acquired-resistant cells. Cell viability was examined using the trypan blue dye exclusion assay. Protein expression was analyzed by western blotting. Somatic mutations in colorectal cancer cells were investigated using the polymerase chain reaction array. PD0325901 and trametinib induced cell death in LoVo and Colo-205 cells but not in DLD-1 and HT-29 cells, which have a PIK3CA mutation constitutively activating Akt and NF-κB. Treatment with PD0325901 and trametinib suppressed ERK1/2 activation in all four cell lines but only induced Akt and NF-κB activation in DLD-1 and HT-29 cells. Inhibition of Akt but not NF-κB, overcame MEK inhibitor resistance in DLD-1 and HT-29 cells. Acquired-resistant LoVo/PR, Colo-205/PR and LoVo/TR cells have constitutively active Akt due to a M1043V mutation in the kinase activation loop of PIK3CA and Akt inhibitor resensitized these cells to MEK inhibitor. These results demonstrate that the overactivation of Akt plays a critical role in MEK inhibitor primary and acquired resistance and implicate combined Akt/MEK inhibition as a potentially useful treatment for RAS/BRAF-mutated colorectal cancer.

Effect of the polysaccharides derived from Dendrobium officinale stems on human HT-29 colorectal cancer cells and a zebrafish model

2021 ◽  
pp. 100995
Author(s):  
Shengchang Tao ◽  
Chunlei Huang ◽  
Zhihong Tan ◽  
Shuna Duan ◽  
Xiaofeng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Dendrobium Officinale ◽  
Zebrafish Model ◽  
Colorectal Cancer Cells ◽  
Ht 29

Crataegus azarolusLeaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells

2015 ◽  
Vol 117 (5) ◽  
pp. 1262-1272 ◽  
Author(s):  
Nadia Mustapha ◽  
Aline Pinon ◽  
Youness Limami ◽  
Alain Simon ◽  
Kamel Ghedira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Cycle Arrest ◽  
Colorectal Cancer Cells ◽  
Hct 116 ◽  
Ht 29

scholarly journals Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation

2014 ◽  
Vol 6 (3) ◽  
pp. 74 ◽  
Author(s):  
Caitlin A Schonewolf ◽  
Monal Mehta ◽  
Devora Schiff ◽  
Hao Wu ◽  
Bruce G Haffty ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Concurrent Chemoradiation ◽  
Colorectal Cancer Cells ◽  
Autophagy Inhibition ◽  
Ht 29

Evaluation of RAC1 Gene Expression Under Exposure Of Plasma Activated Verbascoside in HT-29 Colorectal Cancer Cells

2018 ◽  
Vol 9 ◽  
pp. 36-37
Author(s):  
Kobra Hajizadeh ◽  
Bahram Behzad ◽  
Danial Seifi ◽  
Hassan Mehdian ◽  
Mohammad Nabiouni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cancer Cells ◽  
Colorectal Cancer Cells ◽  
Ht 29

scholarly journals miR-214 sensitizes human colorectal cancer cells to doxorubicin by p53 targeting

2020 ◽  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
P53 Expression ◽  
Colorectal Cancer Cells ◽  
Scratch Wound ◽  
And Migration ◽  
Induced Apoptosis ◽  
Ht 29 ◽  
Human Colorectal Cancer Cells

Objectives: This study aimed to investigate the potential function of miR-214 in the apoptosis induction by targeting p53 in human colorectal cancer cells (CRC) in combination with doxorubicin (DOX). Methods: miR-214 mimics were transfected to HT-29 CRC cells. Following that, the transfected cells were treated with DOX. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and scratch-wound motility assays, respectively. Furthermore, the expression level of miR-214 and p53 was evaluated by qRT-PCR. Results: miR-214 transfection significantly inhibited the cell proliferation rate (P<0.05), induced apoptosis (P<0.05), and harnessed migration (P<0.05) in the HT-29 cells after 48 h. Furthermore, more effectiveness was observed in combination with DOX. Additionally, miR-214 transfection led to a reduction in p53 expression offering that it might be a potential target for miR-214. Conclusion: In conclusion, miR-214 sensitizes HT-29 cells to doxorubicin by targeting p53 indicating the significant role of this miRNA in colorectal cancer chemotherapy.

scholarly journals Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 629-638
Author(s):  
N. N. Bahari ◽  
S. Y. N. Jamaludin ◽  
A. H. Jahidin ◽  
M. N. Zahary ◽  
A. B. Mohd Hilmi
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Colorectal Cancer ◽  
Expression Levels ◽  
Pharmacological Modulation ◽  
Colorectal Cancer Cells ◽  
Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

scholarly journals PLAC1 Enhances Metastatic Potential and is Associated with PI3K/AKT/NF-κB Signaling Pathway in Colon Cancer

2019 ◽  
Author(s):  
JIachi Ma ◽  
Shoukai Zhang ◽  
Danru Liang ◽  
Lei Li ◽  
Jun Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Umbilical Vein ◽  
Metastatic Potential ◽  
Dependent Manner ◽  
Human Colorectal Cancer ◽  
Colorectal Cancer Cells ◽  
Metastatic Process ◽  
Ht 29

Abstract Background: To better explore the underlying mechanism of liver metastatic formation by placenta-specific protein 1 (PLAC1) in human colorectal cancer, we investigated the proliferation, invasion and angiogenic capabilities of human colorectal cancer cell lines with different liver metastatic potentials as well as the mechanism of action of PLAC1 in the metastatic process. Methods: The expression of PLAC1 was detected by reverse transcriptase PCR, western blot and real-time PCR. The effect of PLAC1 on metastatic potential was determined by proliferation, invasion, and angiogenesis assays, including an in vitro coculture system consisting of cancer cells and vascular endothelial cells that were used to detect the relationship between cancer cells and angiogenesis. In addition, we also determined PLAC1 downstream targets that preferentially contribute to the metastatic process. Results: PLAC1 was expressed in HT-29, WiDr and CaCo-2 colorectal cancer cells but not in Colo320 colorectal cancer cells. PLAC1 could not only significantly enhance the proliferation of CoLo320 and human umbilical vein endothelial cells (HUVECs) but could also promote the invasion of CoLo320 cells. The angiogenesis of HUVECs was enhanced by PLAC1 in a dose-dependent manner. In cocultured systems, angiogenesis was significantly increased by coculture with HT-29 cells. In addition, PLAC1 could promote angiogenesis in coculture with HT-29 cells. Furthermore, PLAC1-enhanced metastatic potential of colorectal cancer cells was dependent on activation of the PI3K/Akt/NF-κB pathway. Conclusions: The activation of PI3K/Akt/NF-κB signaling by PLAC1 may be critical for the metastasis of colorectal cancer cells. According to our results, we suggest that modification of PLAC1 function might be a promising new therapeutic approach to inhibit the aggressive spread of colorectal cancer.

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