Kanglaite sensitizes colorectal cancer cells to Taxol via NF-κΒ inhibition and connexin 43 upregulation

Wang, Yijia; Zhang, Chunze; Zhao, Zhenying; Wang, Jiawen; Song, Jiali; Wang, Yue; Liu, Jun; Hou, Shaobin

doi:10.1038/s41598-017-01480-2

Cited by 37 publications

(33 citation statements)

References 39 publications

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“…Cx43 is the most widely expressed connexin in a variety of tissues and is a structural component of GJ . Some reports have shown that paclitaxel inhibits GJ function and Cx43 expression to decrease cytotoxicity of itself . Cx43 as well as other GJ molecules, such as Cx32 and Cx26, has been shown to inhibit primary tumor cell progression.…”

Section: Resultsmentioning

confidence: 99%

“…Gap junction (GJ) function was examined using the "Parachute" dyecoupling assay as described by Wang et al 6 Cells were seeded in six-well plates and grown to 80%-100% confluency. CM-Dil and Calcein-AM were used to determine GJ function.…”

Section: "Parachute" Dye-coupling Assaymentioning

confidence: 99%

“…For this reason, many agents have been used in combination with paclitaxel to challenge resistance . The combination of all‐ trans ‐retinoic acid (ATRA) and paclitaxel has been used to treat a variety of cancers for more than 10 years.…”

Section: Introductionmentioning

confidence: 99%

“…all-trans-retinoic acid, epithelial-mesenchymal transition, gap junction, NF-κΒ, paclitaxel For this reason, many agents have been used in combination with paclitaxel to challenge resistance. 6 The combination of alltrans-retinoic acid (ATRA) and paclitaxel has been used to treat a variety of cancers for more than 10 years. This combination causes more apoptosis and less invasion than paclitaxel alone.…”

Section: Introductionmentioning

confidence: 99%

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All‐trans retinoic acid reverses epithelial‐mesenchymal transition in paclitaxel‐resistant cells by inhibiting nuclear factor kappa B and upregulating gap junctions

Shi

Zheng

et al. 2018

Cancer Science

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Paclitaxel is a widely used chemotherapy drug, but development of resistance leads to treatment failure. Tumor cells that are treated with a sublethal dose of paclitaxel for a long period of time show the epithelial‐mesenchymal transition (EMT) phenotype, which leads to metastasis and resistance. All‐trans retinoic acid (ATRA) is always used in combination with paclitaxel and can reverse EMT in many types of cancer cells. The ability of ATRA to reverse EMT in chemoresistant cells is still unknown. In the present study, the ability of ATRA to reverse EMT in paclitaxel‐resistant cells was investigated. Three colorectal cancer cell lines, HCT116, LoVo and CT26, were treated with sublethal doses of paclitaxel to create resistant cell lines. Western blotting, immunocytochemistry, and “parachute” dye‐coupling assays showed that ATRA reverses EMT, inhibits nuclear factor kappa B (NF‐κΒ), and upregulates gap junctions in paclitaxel‐resistant cells. Scratch wound‐healing and Transwell assays showed that ATRA decreases the migration and invasion abilities of paclitaxel‐resistant cells. In addition, the CT26 cell line was used in the Balb/c pulmonary metastasis model to show that ATRA reduces metastasis of paclitaxel‐resistant cells in vivo. Given these data, ATRA may reverse EMT by inhibiting NF‐κΒ and upregulating gap junctions in paclitaxel‐resistant cells.

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Section: Resultsmentioning

confidence: 99%

Section: "Parachute" Dye-coupling Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

All‐trans retinoic acid reverses epithelial‐mesenchymal transition in paclitaxel‐resistant cells by inhibiting nuclear factor kappa B and upregulating gap junctions

Shi

Zheng

et al. 2018

Cancer Science

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“…p-Akt also upregulates (17) or downregulates (18) the phosphorylation of Cx43 (p-Cx43), depending on the cell type. Phosphorylation is a necessary step for Cx43 to form gap junctions (19), which sensitizes cancer cells to many antitumor drugs (20). However, the nature of the interaction between p-Cx43 and p-Akt in colorectal cancer cells, and whether this interaction affects the cytotoxicity of cetuximab, are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Sensitizes Colorectal Cancer Cells to Cetuximab by Connexin 43 Upregulation-Induced Akt Inhibition

Wang

Wang²,

Wu³

et al. 2020

Front. Oncol.

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Cetuximab is a monoclonal antibody that acts as an anti-epidermal growth factor receptor (EGFR) agent. Cetuximab inhibits the phosphorylation and activation of EGFR and blocks downstream signal pathways of EGF/EGFR, including Ras-Raf-MAPK and PI3K-Akt pathways. Akt activation is an important factor in cetuximab resistance. It has been reported that resveratrol and connexin 43 regulate Akt in different ways based on tissue type. Since connexin 43 interacts with Akt, and resveratrol is known to upregulate connexin 43, we investigated whether resveratrol can sensitize colorectal cancer cells to cetuximab via connexin 43 upregulation. Our work confirmed that resveratrol increases the inhibition of growth by cetuximab in vitro and in vivo, upregulates connexin 43 expression and phosphorylation, increases gap junction function, and inhibits the activation of Akt and NFκB in parental or cetuximab-treated parental HCT116 and CT26 cells. Resveratrol did not exhibit these effects on connexin 43-shRNA transfected cells, so connexin 43 upregulation may contribute to Akt inhibition in these cells. Given these data, resveratrol may sensitize colorectal cancer cells to cetuximab via upregulating connexin 43 to inhibit the Akt pathway.

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MicroRNA‐193a and taxol combination: A new strategy for treatment of colorectal cancer

Hejazi

Baghbani

Amini

et al. 2019

J of Cellular Biochemistry

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Micro RNAs (miRNAs) show a considerable promise as a therapeutic agent for combination therapy of colorectal cancer (CRC). Given that, the current study was purposed to explore the potential therapeutic role and underlying mechanism of miR‐193a as a promising tumor suppressor in human CRC cell lines in combination with Taxol. Therefore, HT‐29 cells with the lowest expression levels of miR‐193a were treated with miR‐193a mimics and Taxol, separately or in combination. Functional analyses showed that the combination therapy inhibited migration and colony formation of HT‐29 cells and arrested the cell cycle at the G1 phase. Moreover, treatment with Taxol reduced cell survival with an increase in mRNA expression of metastasis‐related genes caspase‐3 and caspase‐9, whereas miR‐193a transfection alone didn't significantly influence cell viability and apoptosis induction. Quantitative reverse transcription polymerase chain reaction results also revealed that miR‐193a replacement decreased the expression levels of c‐Myc, MMP‐9, vimentin, and ROCK in treatment groups compared to the controls. Therefore, it could be concluded miR‐193a inactivates cell migration via suppression of metastasis pathways in CRC and through downregulation of c‐Myc, acts as a negative regulator of cell cycle and growth. Then, our findings imply that miR‐193a replacement combined with Taxol chemotherapy could be considered as a new potential therapeutic approach for improvement of CRC treatment.

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Kanglaite sensitizes colorectal cancer cells to Taxol via NF-κΒ inhibition and connexin 43 upregulation

Cited by 37 publications

References 39 publications

All‐trans retinoic acid reverses epithelial‐mesenchymal transition in paclitaxel‐resistant cells by inhibiting nuclear factor kappa B and upregulating gap junctions

All‐trans retinoic acid reverses epithelial‐mesenchymal transition in paclitaxel‐resistant cells by inhibiting nuclear factor kappa B and upregulating gap junctions

Resveratrol Sensitizes Colorectal Cancer Cells to Cetuximab by Connexin 43 Upregulation-Induced Akt Inhibition

MicroRNA‐193a and taxol combination: A new strategy for treatment of colorectal cancer

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