Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the PI3K/AKT signaling pathway

Xu, Jiaman; Zhang, Shouru; Wang, Rong; Wu, Xingye; Zeng, Li; Fu, Zhongxue

doi:10.1042/bsr20160447

Cited by 31 publications

(36 citation statements)

References 24 publications

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“…Inhibition of the PI3K/AKT signaling pathway can reduce insulin-induced chemotherapeutic drug resistance. AKT phosphorylation serves a pivotal part in the activation of the PI3K/AKT/mTOR signaling pathway (36,37).…”

Section: Discussionmentioning

confidence: 99%

Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model

Zhou

et al. 2019

Oncol Lett

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The response of cancer patients to oxaliplatin combined with 5-fluorouracil (5-FU) is difficult to predict. It has been reported that carcinoma-associated fibroblasts (CAFs) could induce AKT and ERK phosphorylation, and upregulate survivin expression in colorectal cancer (CRC) cells, which could lead to oxaliplatin plus 5-FU resistance. A total of 71 patients with advanced CRC (aCRC) treated with oxaliplatin plus 5-FU were included in the present study. These patients comprised 46 chemotherapy responders and 25 non-responders. The expression levels of α-smooth muscle actin (α-SMA), phosphorylated (p)-AKT, p-ERK and survivin were determined by immunohistochemical evaluation of paraffin-embedded samples from patients. A predictive model was established using a Probabilistic Neural Network model. The high expression of α-SMA, p-AKT and survivin in patients with aCRC were associated with oxaliplatin plus 5-FU resistance (P<0.001, P= 0.023 and P= 0.001, respectively). Furthermore, patients with stage IV CRC exhibiting high expression levels of α-SMA and survivin experienced a reduced progression-free survival time compared with patients with low expressions of α-SMA and survivin (5.5 vs. 15.0 months; 5.5 vs. 15.0 months; P=0.005 and P=0.001, respectively). Stage IV CRC and high survivin expression predicted a reduced overall survival time compared with that for patients with stage IV CRC and low survivin expression (50.0 vs. 15.0 months; P<0.001). Patients with α-SMA, p-AKT, p-ERK and survivin overexpression were more likely to present with intrinsic resistance to the oxaliplatin plus 5-FU regimen (the accuracies of modeling, validation and prediction were 83.7, 92.9 and 85.7%, respectively). In conclusion, the multifactorial predictive biomarker model of α-SMA, p-AKT, p-ERK and survivin expression for patients with aCRC to predict intrinsic resistance to oxaliplatin plus 5-FU regimens is of great efficiency and accuracy. Patients with high expression of this predictive model may be intrinsically resistant to the oxaliplatin and 5-FU regimen.

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Section: Discussionmentioning

confidence: 99%

Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model

Zhou

et al. 2019

Oncol Lett

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“…In the current study, we demonstrated that downregulation of PRDX2 significantly 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 Q1 10 0 10 4 10 3 10 2 10 1 10 0 10 4 10 3 10 2 10 1 10 0 (e) It is known that besides proliferation, apoptosis also plays a crucial role in the development of cancer, and dysregulated apoptosis is a major feature of tumor cells. PRDX2 has been confirmed to regulate tumor cell apoptosis [19]. Herein, we found that a decrease in PRDX2 expression resulted in an increase in apoptosis in NSCLC cells, but had no significant effect on apoptosis in BEAS-2B cells.…”

Section: Discussionmentioning

confidence: 66%

“…It has been identified that PRDX2 is overexpressed in various type of cancers including colorectal cancer [30] and cervical cancer [31] and associated with the tumor metastasis and prognosis of patients [22]. Knockdown of PRDX2 could inhibit the growth and promote apoptosis of colorectal cancer cells and increase the sensitivity of colon cancer cells to 5-FU [19,21]. However, PRDX2 is considered to perform an inconsistent function in hepatocellular carcinoma (HCC).…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the Akt/mTOR signaling pathway is capable of regulating the expression of downstream effectors, such as Cyclin D1 and p70S6k, participating in cellular functions. More importantly, it has been revealed that PRDX2 regulates the resistance of colon cancer cells to 5-FU by regulating the Akt signaling pathway [19]. To determine whether PRDX2 impacts the Akt/mTOR signaling pathway in NSCLC cells, we examined the expression of important components of this signaling pathway in the siRNA-PRDX2 transfected cells.…”

Section: Discussionmentioning

confidence: 99%

“…As a key member of PRDXs family, peroxiredoxin 2 (PRDX2) has been reported to scavenge peroxides and reactive oxygen species (ROS) in cells to regulate redox status, thus participating in a variety of cellular biological functions [14][15][16]. Recent studies identify aberrant expression of PRDX2 in several types of cancers and demonstrate that PRDX2 exerts an important role in cell proliferation, death, and drug sensitivity of cancer [17][18][19][20]. For example, it has been indicated that PRDX2 is upregulated in colorectal cancer and exerts a tumor promoting role in the progression of colorectal cancer [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Silencing of PRDX2 Inhibits the Proliferation and Invasion of Non-Small Cell Lung Cancer Cells

Ai-jun

et al. 2020

BioMed Research International

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Peroxiredoxin 2 (PRDX2), a member of the peroxiredoxin family of antioxidant enzymes, has been revealed to be an important player in cancer progression. However, the biological role of PRDX2 in the progression of non-small cell lung cancer (NSCLC) is poor reported. In the present study, the loss-of-function experiments were performed to investigate the specific role of PRDX2 in the growth and invasion of NSCLC. The results revealed that knockdown of PRDX2 by siRNA interference significantly suppressed the proliferation, migration, and invasion of A549 and H1299 cells, as well as diminished the activity of MMP9. Additionally, the decrease in PRDX2 expression significantly promoted apoptosis in NSCLC cells by downregulating expression of Bcl-2 and upregulating the expression of Bax, cleaved caspase 3 and cleaved caspase 9, but had no significant effect on the apoptosis of normal lung epithelial cells BEAS-2B. Moreover, PRDX2 inhibitor also inhibited the proliferation, migration, and invasion of A549 cells and promoted apoptosis. Further, our data demonstrated that silencing of PRDX2 markedly reduced the phosphorylation of Akt and mTOR and expression of downstream proteins Cyclin D1 and p70S6k. In conclusion, our findings indicate that PRDX2 exerts a prooncogenic role in the progression of NSCLC and might be a potential therapeutic target for NSCLC treatment.

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Peroxiredoxin of Arthrospira platensis derived short molecule YT12 influences antioxidant and anticancer activity

Sannasimuthu

Ramani

Pasupuleti

et al. 2020

Cell Biology International

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This study demonstrates both the antioxidant and anticancer potential of the novel short molecule YT12 derived from peroxiredoxin (Prx) of spirulina, Arthrospira platensis (Ap). ApPrx showed significant reduction in reactive oxygen species (ROS) against hydrogen peroxide (H 2 O 2) stress. The complementary DNA sequence of ApPrx contained 706 nucleotides and its coding region possessed 546 nucleotides between position 115 and 660. Real-time quantitative reverse transcription polymerase chain reaction analysis confirmed the messenger RNA expression of ApPrx due to H 2 O 2 exposure in spirulina cells at regular intervals, in which the highest expression was noticed on Day 20. Cytotoxicity assay was performed using human peripheral blood mononuclear cells, and revealed that at 10 μM, the YT12 did not exhibit any notable toxicity. Furthermore, ROS scavenging activity of YT12 was performed using DCF-DA assay, in which YT12 scavenged a significant amount of ROS at 25 μM in H 2 O 2-treated blood leukocytes. The intracellular ROS in human colon adenocarcinoma cells (HT-29) was regulated by oxidative stress, where the YT12 scavenges ROS in HT-29 cells at 12.5 μM. Findings show that YT12 peptide has anticancer activity, when treated against HT-29 cells. Through the MTT assay, YT12 showed vital cytotoxicity against HT-29 cells. These finding suggested that C Cell ell B Biology iology I International nternational Abbreviations: Ap, Arthrospira platensis; Cp, peroxidatic cys; DCF-DA, 2′,7′-dichlorofluorescein diacetate; H 2 O 2 , hydrogen peroxide; HT-29, human colon adenocarcinoma cell; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PBMC, human peripheral blood mononuclear cell; Prx, peroxiredoxin; TEAC, Trolox equivalent antioxidant capacity.

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Knockdown of PRDX2 sensitizes colon cancer cells to 5-FU by suppressing the PI3K/AKT signaling pathway

Cited by 31 publications

References 24 publications

Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model

Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model

Silencing of PRDX2 Inhibits the Proliferation and Invasion of Non-Small Cell Lung Cancer Cells

Peroxiredoxin of Arthrospira platensis derived short molecule YT12 influences antioxidant and anticancer activity

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