Document Details
|
Document Type |
: |
Thesis |
|
Document Title |
: |
THE POTENTIATING EFFECT OF 5-FLUROURCIL WITH SIMVASTATIN IN COLORECTAL CANCER CELLS THROUGH COMBINED NANO-STRUCTURE FORMULA. التأثير المحفز للـ -5فلورويوراسيل مع سيمفاستاتين في خلايا سرطان القولون والمستقيم من خلال الجمع بينهم بهيكل نانو. |
|
Subject |
: |
Faculty of medicine |
|
Document Language |
: |
Arabic |
|
Abstract |
: |
Background: Colorectal cancer (CRC) is the most influential cause of cancer death worldwide. Its death rate and incidence have been increasing over 20 years in Saudi Arabia. 5-Fluorouracil (5-FU) is an active cytotoxic agent in different kinds of tumors. Despite its effectiveness in CRC therapy, its clinical applications are narrowed because of its short half-life, resistance, and side effects. Statins are inhibitors of β- Hydroxy-β-methylglutaryl CoA (β-HMG-Co A). reductase. They reduce cholesterol biosynthesis by altering the formation of mevalonate, making them potentially antineoplastic agents. Due to the high dose required for inhibition of proliferation which may be associated with significant toxicity, their antineoplastic use has not established, yet. Aim: this study was directed to formulate nanoparticles of 5-FU in the presence of Simvastatin (SMV) in an attempt to enhance the therapeutic efficacy and may reduce 5-FU toxicity. Methods: a solid lipid nanoparticles (SLN) formulated and assayed for particle size, stability, morphology, entrapment efficiency and drug release. Through used human colorectal cancer cell line (HCT-116), the IC50 was investigated to evaluate the cytotoxicity, apoptosis induction, cell cycle distribution, and the intercellular reactive oxygen species (ROS) after treatment with SLN 5-FU and/or SMV Compared with raw drug. Results: The particles size was (107-117nM) and stability of formula between (-5.53, -14 mV), entrapment efficiency was 80-97.5% for 5-FU and SMV respectively. Raw 5-FU had IC50 12.69μM while cell treated with 5-FU SLN, IC50 dropped to 5.98μM and addition of 5μM SMV SLN, IC50 was significantly reduced to 1.582μM. Also, treatment with SLN 5-FU alone or/and SMV significantly accumulated the cells in sub-G1 and dramatically increased the percentage of Late apoptotic cells significantly in comparison to raw 5-FU. Moreover, SMV SLN with 5-FU increased intracellular ROS by 145.2 %. Conclusion, a significant effect of SLN among treatment with 5-FU and / or SMV against HCT-116 cell line. |
|
Supervisor |
: |
Dr. Fatemah Omar Kamel |
|
Thesis Type |
: |
Master Thesis |
|
Publishing Year |
: |
1441 AH
2020 AD |
|
Co-Supervisor |
: |
Prof. Osama Abdelhakim Ali Ahmed |
|
Added Date |
: |
Thursday, January 23, 2020 |
|
Researchers
| حنين صميدان الجهني | Aljehani, Hanin Sumaydan | Researcher | Master | |
|
Back To Researches Page
|