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Abstract: Colorectal cancer (CRC) is the third most common cancer, and its mortality rate ranks second among all cancers
.
The incidence of CRC among young adults under the age of 50 is particularly severe, with an annual increase of 2.
2% since 1995
.
The treatment of colorectal cancer is a complex and systematic process.
The current standard therapies include surgery, chemotherapy, radiotherapy, and targeted therapy.
The 5-year relative survival rate of CRC patients is 65%; however, it declines in patients with stage IV CRC.
To 12%
.
The clinical treatment of colorectal cancer has always been faced with clinical difficulties such as the scarcity of highly effective and specific targeted drugs, the low effective rate of chemotherapeutics and the large side effects, and the reversal of chemotherapy resistance, which have severely restricted the improvement of the prognosis of CRC patients
.
Therefore, understanding the pathogenesis of CRC and developing new therapies are unmet clinical needs of CRC patients
.
Keywords: NK-1R; endoplasmic reticulum stress; MAPK signaling pathway; chemotherapy resistance; colorectal cancer Professor Fu Caiyun's research team from Zhejiang Sci-Tech University School of Life Sciences and Medicine discovered nerves that are clinically used to treat nausea and vomiting after chemotherapy Kinin receptor 1 (NK-1R) antagonists can induce apoptosis of colorectal cancer cells in vitro and in vivo, and its molecular mechanism is through endoplasmic reticulum stress, ERK signal inactivation, and downstream c-Myc protein degradation.
The new mechanism of PERK-eIF2α-ATF4-CHOP endoplasmic reticulum stress signal axis mediated cytotoxicity mediated by PERK-eIF2α-ATF4-CHOP helps to enhance the chemosensitivity of colorectal cancer cells and the resistance of reverse transformation therapy
.
In this work, the researchers first found that NK-1R was significantly highly expressed in tumor tissue sections of patients with colorectal cancer and colorectal cancer cell lines.
The NK-1R antagonist SR140333 and aprepitant were used to block NK.
-1R significantly inhibits the proliferation of colorectal cancer cells in vivo and in vitro and induces apoptosis.
This apoptosis-inducing effect is through the release of endoplasmic reticulum calcium and the activation of the PERK-ATF4-CHOP endoplasmic reticulum stress signaling pathway, followed by inhibition of ERK -mediated by c-Myc signal transduction
.
More importantly, blocking NK-1R increases the sensitivity of colorectal cancer cells to chemotherapy drugs, and overcomes the resistance to chemotherapy drugs in vitro and in vivo by inducing endoplasmic reticulum stress and inhibiting the ERK-c-Myc signaling pathway.
Medicinal properties
.
This work proved that NK-1R antagonists inhibit tumor growth and enhance chemosensitivity through a new mechanism that induces endoplasmic reticulum stress in human CRC cells
.
These novel discoveries expand people's understanding of the downstream molecular events of NK-1R-mediated GPCR signal transduction, provide new targets and new drugs for the diagnosis and treatment of colorectal cancer, and also provide a clinical application of the old aprepitant drug The new use to benefit patients with new-onset colorectal cancer and relapsed drug resistance provides a solid theoretical basis
.
It is reported that Professor Fu Caiyun, School of Life Sciences, Zhejiang Sci-Tech University, is the only corresponding author of this article
.
Postgraduate student Shi Yue under the guidance of Professor Fu Caiyun (graduate of 2015, currently studying for a doctorate degree at West Lake University), Director Wang Xi of the 903rd Hospital of the People’s Liberation Army, and postgraduate students Meng Yueming and Ma Junjie under the guidance of Professor Fu Caiyun are the co-first authors of this article
.
This research was also supported by Dr.
Jian Kang from the Peter MacCallum Cancer Centre in Australia and Professor Yihai Cao from the Karolinska Institute in Sweden
.
WILEY Paper Information: A Novel Mechanism of Endoplasmic Reticulum Stress- and c-Myc-Degradation-Mediated Therapeutic Benefits of Antineurokinin-1 Receptor Drugs in Colorectal CancerYue Shi,Xi Wang,Yueming Meng,Junjie Ma,Qiyu Zhang,Gang Shao,Lingfei Wang ,Xurui Cheng,Xiangyu Hong,Yong Wang,Zhibin Yan,Yihai Cao,Jian Kang,Caiyun Fu,Advanced Science DOI: 10.
1002/advs.
202101936 Click "Read the original text" in the lower left corner to view the original text of the paper
.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley is a high-quality open source journal founded in 2014.
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