双重向Bcl-2和Bcl-xL增加了骨髓瘤对多克索鲁比的反应
Chuanhua Cao1,2, Yu Pei1,2, Haiying Yu1,2
1Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, People's Republic of China.
Journal of chemotherapy (Florence, Italy)
|June 13, 2023
概括
纳维托克拉克斯是一种BCL-2/BCL-xL抑制剂,可以克服骨髓瘤的化疗耐药性. 使用纳维托克拉克斯同时抑制Bcl-2和Bcl-xL,对治疗耐化学药性骨髓瘤有希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 化疗耐药性是骨髓瘤治疗失败的主要原因.
- 制定提高骨髓瘤对化疗敏感性的策略,对于改善患者的治疗结果至关重要.
研究的目的:
- 为了研究纳维托克拉克斯,Bcl-2/Bcl-xL的选择性抑制剂,在克服骨髓瘤的化疗耐药性的疗效.
- 探索将纳维托克拉克斯与多克索鲁比辛结合用于骨髓瘤治疗的潜力.
主要方法:
- 在抗多克索鲁比骨髓瘤细胞中评估了Bcl-2和Bcl-xL的表达.
- 评估了单独或联合使用的纳维托克拉克斯,维尼托克拉克斯和多克索鲁比辛对骨髓瘤细胞活性的影响.
- 利用对多克索鲁比敏感和耐药骨髓瘤的小鼠模型来确认体内疗效.
主要成果:
- 在耐多克索鲁比骨髓瘤细胞中,BCL-2被上调,但单独抑制BCL-2是不够的.
- 同时抑制Bcl-2和Bcl-xL显著降低了耐药细胞的活力.
- 在体外和体外模型中,Navitoclax在克服多克索鲁比耐药性方面表现出有效性,与多克索鲁比具有协同效应.
结论:
- 同时抑制Bcl-2和Bcl-xL是一种新的策略,可以使耐化疗骨髓瘤细胞敏感.
- 纳维托克拉克斯 (Navitoclax) 与多克索鲁比辛 (doxorubicin) 结合,为骨髓瘤提供了一个有前途的治疗方法,需要进一步的临床研究.
更多相关视频
08:57Sample Extraction and Simultaneous Chromatographic Quantitation of Doxorubicin and Mitomycin C Following Drug Combination Delivery in Nanoparticles to Tumor-bearing Mice
Published on: October 5, 2017
11.0K
09:19Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
8.7K
相关概念视频
02:57Targeted Cancer Therapies
7.7K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
7.7K
02:50Combination Therapies and Personalized Medicine
5.0K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.0K
02:56Treatment Resistant Cancers
3.4K
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.4K
01:31The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K