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发表于 2022-6-12 16:04:45 | 显示全部楼层 |阅读模式
The overall 5-year survival rate of patients with human pancreatic cancer remains less than 8% because of its aggressive growth, early metastasis and resistance to conventional chemoradiotherapy. It is essential to develop innovative and effective therapeutic agents to improve its prognosis. DMZ is extracted from the xylem of Traditional Chinese medicine. Our study aimed to assess the effects of DMZ on cell proliferation and its role in the chemosen- sitivity to gemcitabine in human pancreatic cancer cells. The effects of DMZ on cancer cell proliferation, cell cycle distribu- tion, apoptosis and autophagy were evaluated in various human pancreatic cancer cell lines, and the antitumor effects of DMZ alone and in combination with gemcitabine were identified in a xenograft mouse model. The results showed that DMZ could inhibit the proliferation of pancreatic cancer cells and arrest cell cycle at G0/G1 phase by regulating the expression of Cyclin D1 and Cyclin A2. Moreover, DMZ killed pancreatic cancer cells through two different mechanisms: inducing autopha- gic cell death at low concentrations and apoptotic cell death at high concentrations. Furthermore, DMZ could enhance the chemosensitivity of pancreatic cancer cells to gemcitabine both in vitro and in vivo through modulation of the cross talk between autophagy and apoptosis. DMZ is a potential therapeutic agent for developing novel therapeutic strategies in human pancreatic cancer.
International Journal of Cancer
DMZ inhibits cell growth andenhances cell chemosensitivity to gemcitabine in human pancreatic cancer cells via apoptotic and autophagic pathways
1 Department of General Surgery, Peking University First Hospital, Beijing, People’s Republic of China
2 Department of Endoscopy Center, Peking University First Hospital, Beijing, People’s Republic of China
3 Department of Pharmaceutical Chemistry, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
Pancreatic cancer (PC) is the fourth leading cause of cancer- related death in the United States. The overall 5-year survival
rate remains <8% and has not improved significantly for sev- eral decades.1,2 The dismal outcome of PC is due to its aggressive growth, early metastasis and resistance to
Key words: DMZ, chemosensitivity, apoptosis, autophagy, pancre- atic cancer
Conflict of interest: No potential conflicts of interest were disclosed.
F.W. and X.T. are first authors and contributed equally to this work Grant sponsor: National Natural Science Foundation of China; Grant numbers: 81372605, 81572339, 81672353; Grant sponsor: National High Technology Research and Development Program of China; Grant number: SS2015AA020405
DOI: 10.1002/ijc.31211
History: Received 16 Mar 2017; Accepted 5 Dec 2017; Online 14 Dec 2017
conventional chemoradiotherapy. Efforts have been made to investigate the effects of the combination of different chemo- therapeutics, but the results have not been satisfactory.3 To date, gemcitabine remains the first-line chemotherapeutic agent for PC, though the response rate remains low.4 It is essential to develop innovative and effective therapeutic agents to improve the prognosis of PC, and an important part of this process is determining the mechanisms of cell death induced by potential therapeuticagents.
Apoptosis is a programmed cell death process regulated by specific genes. As an important form of cell death, apo- ptosis plays an important role in the maintenance of the nor- mal physiologic function of cells.5 In cancerous cells, apoptosis is inhibited to a large extent to maintain the unre- strained growth of the cancer. Many chemotherapeutics, including gemcitabine, can induce apoptosis in cancerous cells to exert their antitumor effect.6 Autophagy is another essential process that allows cells to maintain the protein metabolic balance and cellular homeostasis. Autophagy is activated during environmental stress, such as nutrient star- vation or hypoxia, and promotes cell survival.7 However, excessive autophagy is also responsible for inducing cell death. Autophagy-induced cell death is caspase independent, which is similar to the apoptosis-inducing factor (AIF) induced apoptotic cell death, and nuclear fragmentation is
Int. J. Cancer:
Cancer Therapy and Prevention
 楼主| 发表于 2022-6-12 16:11:34 | 显示全部楼层
  ヒト膵臓がん患者の全5年生存率は、その積極的な成長、早期転移、および従来の化学放射線療法に対する耐性のため、8%未満のままです。予後を改善するための革新的で効果的な治療薬の開発が不可欠です。DMZが抽出されます。伝統的な中国医学のxylemから。私たちの研究は、細胞増殖に対するDMZの効果と、ヒト膵臓癌細胞におけるゲムシタビンに対する化学感受性におけるその役割を評価することを目的としました。癌細胞増殖、細胞周期分布に対するDMZの効果。 、アポトーシスおよびオートファジーは、さまざまなヒト膵臓癌細胞株で評価され、DMZ単独およびジェムシタビンとの併用の抗腫瘍効果が異種移植マウスモデルで同定されました。結果は、DMZが膵臓癌細胞の増殖を阻害し、細胞を停止できることを示しました。サイクリンD1とサイクリンA2の発現を調節することによりG0/G1期で循環します。さらに、DMZは膵臓を殺しました低濃度での自食作用による細胞死と高濃度でのアポトーシス細胞死の2つの異なるメカニズムによる反応性癌細胞DMZは、ヒト膵臓癌における新しい治療戦略を開発するための潜在的な治療薬です。
DOI:10.1002 / ijc.31211
従来の化学放射線療法。さまざまな化学療法の組み合わせの効果を調査するための努力がなされてきましたが、結果は満足のいくものではありませんでした。 4 PCの予後を改善するには、革新的で効果的な治療薬を開発することが不可欠であり、このプロセスの重要な部分は、潜在的な治療薬によって誘発される細胞死のメカニズムを決定することです。
Hito suizō gan kanja
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