Combination therapy application of Abemaciclib with Doxorubicin in triple negative breast cancer cell line MDA-MB-231

Synergistic Effect of Doxorubicin and Abemaciclib



Triple Negative Breast Cancer, TNBC, Abemaciclib, Doxorubicin, Combination Therapy


Due to lack of clinical biomarkers, Triple Negative Breast Cancer (TNBC) is more likely to have spread to other tissues at time of diagnosis and therapy planning generally involves use of cytotoxic chemotherapy agents, such as Doxorubicin. We aimed to investigate possible advantages of using combination strategy using Doxorubicin alongside Abemaciclib. After determining the IC50 values for Doxorubicin (DOX) and Abemaciclib (ABE); CompuSyn and ComBenefit software were used to reveal the effect resulting from the combination of two drugs. Following the determined effect, cell death was revealed by fluorescence microscopy and a colony forming assay was performed to see the potential of even a single cancer cell with adhesive character to survive over time and form a clone of itself. Detection of changing antioxidant activity following DOX, ABE and DOX+ABE combination therapy in MDAMB231 cells was determined by measuring MDA, SOD and GSH activities. The expression of Cleaved Caspase 3, PARP, Cleaved PARP, Cdk2 and Bax, which changed as a result of DOX, ABE and DOX+ABE application, was shown by Western Blotting.Cyclin-dependent kinase inhibitors appear as promising agents in therapy planning for breast cancer due to their prominent role in cell cycle regulation, where the number of studies interrogating its efficiency in the treatment of cancer such as TNBC is limited. For this reason, in this study, we aimed to determine the impact of the combined use of the CDK4/6 inhibitors ABE and DOX on the cytotoxicity, apoptotic homeostasis, alterations in antioxidative mechanisms, and the molecular pathways that they utilize. Our results showed that when used in combination, Doxorubicin and Abemaciclib showed a synergistic effect on TNBC cell line MDA-MB-231.

Author Biographies

Tugce Nur Eralp, Yildiz Technical University, Graduate School of Science and Engineering, Department of Molecular Biology and Genetics, Istanbul, 34220, Turkey

I graduated from the Molecular Biology and Genetics department with Honors Degree. While I was studying at university, I also worked on and did a project on Bag1 protein roles on cervical cancer with the support of The Scientific And Technological Research Council Of Turkey, 2209-A - Research Project Support Program for Undergraduate Students between the 2nd and 4th year of my degree. After my undergraduate graduation; While continuing my master's degree at YTU Genetics, I also participated as a scholar in a project related to the development of monoclonal antibodies for the early diagnosis of cystic fibrosis at The Scientific And Technological Research Council Of Turkey, Marmara Research Center on Gebze campus. Immediately after starting my doctorate at Yildiz Technical University, I worked as a research assistant at Altınbaş University Faculty of Medicine, Medical Biology and Genetics for 4 years. While I was continuing my doctorate, I quit my job and moved to Genetic Diseases Assessment Center and I have been working here for 2 years and continuing my doctorate. Here, I work to bring Noninvasive Prenatal Screening Tests, whole exome sequencing analyses, cancer tests and all other genetic tests to our country. I have 13 years of experience in academic and industry fields.

Akin Sevinc, Izmir Genetic Diseases Assessment Center, Izmir, 35220, Turkey

Interdisciplinary professional with 22 years of experience in Human Molecular Genetics (M.Sc.); Molecular Biology and Biochemistry (Ph.D.); and a graduate-level background in Finance & Management (M.B.A). CFA Level I Candidate.

Utilizing a unique blend of technical, research and analytical skills from academic and research experiences, aiming to become a key player in equity research field. With highly developed organizational skills, able to succeed expectations in fast-paced collaborative team-work environments.

Areas of Expertise:

Private Equity Research and M&A Analysis
Due Diligence, and Quantitative Data Analysis
Building & Maintaining Financial Models, Valuation
Leadership, Talent Acquisition, and Supervision
Molecular Biology and Genetics Research
Advances in Healthcare and Pharmacology
Genetics and Epidemiology of Human Cancers
Biochemistry and Protein Chemistry
Biophysical and Biochemical Research

Banu Mansuroglu, Yildiz Technical University, Faculty of Science and Letters, Department of Molecular Biology and Genetics, Istanbul, 34220, Turkey

Institutional Information: Prof.Dr., Faculty Of Arts & Science, Department Of Molecular Biology And Genetics, General Biology  Research Areas: Moleculer Biology of Cancer, Biochemistry, Biomolecules, Molecular Biochemistry, Biotechnology, Biomaterial, Molecular Biology and Genetics,  Natural Sciences, Life Sciences





Original Research Articles