Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway.
Cabazitaxel suppresses colorectal cancer cell growth via enhancing the p53 antitumor pathway.
复制标题
卡巴他赛通过增强 p53 抗肿瘤途径抑制结直肠癌细胞生长
DOI：
10.1002/2211-5463.13290
复制
发表时间：
2021-11
期刊：
影响因子：
2.6
通讯作者：
Yuan P
中科院分区：
文献类型：
--
作者：
Zhang W;Sun R;Zhang Y;Hu R;Li Q;Wu W;Cao X;Zhou J;Pei J;Yuan P
2020年，结直肠癌约有193万新发病例和94万例死亡。结直肠癌的一线化疗药物主要以5-氟尿嘧啶为主，但这些药物的使用因耐药性的产生而受到限制。因此，需要新的化疗药物来有效治疗结直肠癌患者。在本研究中，我们筛选了美国食品药品监督管理局批准的 160 种药物，发现微管抑制剂卡巴他赛 (CBT) 可以在体外抑制结直肠癌细胞的集落形成和细胞迁移。 CBT 还诱导结直肠癌细胞的 G2/M 期停滞和凋亡。最重要的是，它抑制体内结直肠癌细胞异种移植肿瘤的生长。 RNA 测序转录组分析表明，Tub 家族基因在 CBT 处理的结直肠癌细胞中表达异常。 CBT 在结直肠癌细胞中诱导与细胞周期停滞、细胞凋亡以及抑制血管生成和转移相关的几个 p53 下游基因的表达。总的来说，我们的结果表明，CBT 通过上调 p53 通路来抑制结直肠癌，因此 CBT 可能有潜力作为结直肠癌的替代化疗药物。在本研究中，我们筛选了美国食品药品监督管理局批准的 160 种药物，旨在寻找用于结直肠癌 (CRC) 治疗的新型化疗药物。我们发现微管抑制剂卡巴他赛 (CBT) 在体外和体内对 CRC 细胞均具有抑制作用。转录组分析显示，CBT 通过上调 p53 通路诱导 CRC 细胞凋亡，这意味着 CBT 可能具有治疗 CRC 患者的化疗潜力。
There were approximately 1.93 million new cases and 940 000 deaths from colorectal cancer in 2020. The first‐line chemotherapeutic drugs for colorectal cancer are mainly based on 5‐fluorouracil, although the use of these drugs is limited by the development of drug resistance. Consequently, there is a need for novel chemotherapeutic drugs for the efficient treatment of colorectal cancer patients. In the present study, we screened 160 drugs approved by the Food and Drug Administration and identified that cabazitaxel (CBT), a microtube inhibitor, can suppress colony formation and cell migration of colorectal cancer cells in vitro. CBT also induces G2/M phase arrest and apoptosis of colorectal cancer cells. Most importantly, it inhibits the growth of colorectal cancer cell xenograft tumors in vivo. Transcriptome analysis by RNA‐sequencing revealed that Tub family genes are abnormally expressed in CBT‐treated colorectal cancer cells. The expression of several p53 downstream genes that are associated with cell cycle arrest, apoptosis, and inhibition of angiogenesis and metastasis is induced by CBT in colorectal cancer cells. Overall, our results suggests that CBT suppresses colorectal cancer by upregulating the p53 pathway, and thus CBT may have potential as an alternative chemotherapeutic drug for colorectal cancer. In the present study, we screened 160 drugs approved by the Food and Drug Administration, aiming to identify novel chemotherapeutic agents for colorectal cancer (CRC) treatment. We identified that the microtubule inhibitor cabazitaxel (CBT) has a suppressive effect on CRC cells both in vitro and in vivo. Transcriptome analysis revealed that CBT induced apoptosis in CRC cells by upregulating the p53 pathway, implying that CBT may hold chemotherapeutic potential for the treatment of patients with CRC.
登录
查看更多内容
影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
DOI：
10.6004/jnccn.2018.0061
发表时间：
2018-07
期刊：
Journal of the National Comprehensive Cancer Network : JNCCN
影响因子：
--
作者：
Benson AB;Venook AP;Al-Hawary MM;Cederquist L;Chen YJ;Ciombor KK;Cohen S;Cooper HS;Deming D;Engstrom PF;Grem JL;Grothey A;Hochster HS;Hoffe S;Hunt S;Kamel A;Kirilcuk N;Krishnamurthi S;Messersmith WA;Meyerhardt J;Mulcahy MF;Murphy JD;Nurkin S;Saltz L;Sharma S;Shibata D;Skibber JM;Sofocleous CT;Stoffel EM;Stotsky-Himelfarb E;Willett CG;Wuthrick E;Gregory KM;Gurski L;Freedman-Cass DA
通讯作者：
Freedman-Cass DA
卡巴他赛通过 PI3K/Akt/mTOR 途径诱导的自噬导致 A549 细胞死亡
影响因子：
3.4
作者：
Huo R;Wang L;Liu P;Zhao Y;Zhang C;Bai B;Liu X;Shi C;Wei S;Zhang H
通讯作者：
Zhang H
影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
45.3
作者：
Kopetz, Scott;Chang, George J.;McWilliams, Robert R.
通讯作者：
McWilliams, Robert R.