Multicenter randomized study on Me-CCNU, 5-FU and ADM<i>vs</i>ACNU, 5-FU and ADM for treatment of advanced gastric cancer

Xiao, Shu–Dong; Li, Dehua; De-zhong, Zhang; Shen, Mou-Ji; Zhu, Xiaoting; He, Guifen; Zhao, Tong; Li, Leping; Deng, X H; Wang, Min; Wang, Xiuling; Chen, Qiang; Zhang, Yongping; Yao, Cui-Ling; Bao, Junzhe; Guo-wei, Tong; Zhu, Liang-Fa; Jiang, Hao; Kurihara, Minoru

doi:10.3748/wjg.v3.i4.238

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“…However, the side effects of DOX, including cardiotoxicity and bone marrow suppression, restrict its use in clinical practice [4]. Therefore, the combined use of multiple chemotherapeutic drugs can help reduce the dosage of DOX and avoid the occurrence of DOX-induced side effects [5][6][7][8]. However, the clinical use of chemotherapeutic drugs has certain toxic side effects and it is important to seek a new DOX treatment method to reduce the dosage of DOX without affecting its therapeutic effect.…”

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confidence: 99%

Regulatory effect of peroxiredoxin 1 (PRDX1) on doxorubicin-induced apoptosis in triple negative breast cancer cells

et al. 2022

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Patients with triple negative breast cancer (TNBC) lack the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2; thus, conventional hormone and targeted therapies have minimal effect on them. Therefore, clinical treatment of TNBC is still based on chemotherapy and supplemented by other methods. Doxorubicin (DOX), a common drug used in TNBC chemotherapy, has high affinity for cardiolipin, and the nematosomes are rich in cardiolipin; therefore, DOX has high mitochondria-targeting ability. DOX accumulates and plunders the electrons of nicotinamide adenine dinucleotide phosphate (NADPH) and cytochrome C in mitochondria to produce semiquinone DOX. Under the action of oxygen molecules, semiquinone DOX is reduced to DOX and reactive oxygen species (ROS) are generated. The accumulation of ROS can cause mitochondrial dysfunction and lead to mitochondrial dependent apoptosis. Bioinformatic analysis of samples from TNBC patients revealed that peroxiredoxin 1 (PRDX1) was highly expressed in TNBC tissues, and the poor prognosis of patients with high PRDX1 expression was considerably increased. Previous studies determined that DOX can upregulate the expression of the PRDX1 protein in the human TNBC cell line (MDA-MB-231). Thus, we speculate that PRDX1 plays an important role in the process of DOX-induced TNBC cell apoptosis. In this study, we aimed to explore the role of PRDX1 in the process of DOX-induced TNBC cell apoptosis. We found that PRDX1 deletion increased the sensitivity of MDA-MB-231 cells to DOX, which was mainly due to mitochondrial oxidative stress caused by intracellular ROS accumulation, leading to mitochondria-dependent apoptosis. Deletion of PRDX1 promotes the PI3K/Akt signaling pathway to mediate the expression of GSK3β. Gsk3β is an upstream signal of mitochondria-dependent apoptosis, and is also an important target of ROS. PRDX1 participates in adriamycin-induced apoptosis of TNBC cells by regulating the expression level of GSK3β. Our findings present new insights to treat breast cancer and TNBC, outlines the clinical use of DOX, and provides a basic theory to develop PRDX1 gene function.

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