Chromosomal instability reducing effect of paclitaxel and lapatinib in mouse embryonic stem cells with chromosomal abnor
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ORIGINAL ARTICLE
Chromosomal instability reducing effect of paclitaxel and lapatinib in mouse embryonic stem cells with chromosomal abnormality Banafsheh Mirzaei‑Seresht1,2 · Masood Bazrgar1 · Masoud Sheidai2 · Seyedeh‑Nafiseh Hassani3 · Najmeh Sadat Masoudi1 · Sepideh Mollammohammadi3 Received: 3 April 2020 / Accepted: 7 October 2020 © Springer Nature B.V. 2020
Abstract Chromosomal abnormalities, as a frequent phenomenon in cultured embryonic stem cells (ESCs), is a major obstacle in the ESC application in regenerative medicine. Recent studies showed that aneuploid embryonic stem cells of humans and mice are more vulnerable to anticancer drugs, compared with normal cells. The aim of the current study was to evaluate effects of three anticancer drugs, paclitaxel, lapatinib and bortezomib, on mouse embryonic stem cells (mESCs) as a suitable and available model. To assess in vitro cell toxicity, two mESC lines were treated with the aforementioned drugs. Using G-band karyotyping and micronucleus assay, the effect of anticancer drugs in terms of reduction of chromosomal instability in the mESCs was evaluated in control and treatment groups. Also, apoptosis rate of both groups was estimated by FITC-Annexin V/ Propidium Iodide (PI) double staining. In addition, the effect of these three drugs in maintaining the pluripotency was assessed through alkaline phosphatase assay and quantification of the expression of three key pluripotency genes, Nanog, Pou5f1 and Sox-2 was performed using Real Time PCR. The rate of numerical abnormalities after treatment with paclitaxel and lapatinib was lower than the control group. The expression level of pluripotency genes exhibited no significant difference between control and treatment groups. Administration of paclitaxel and lapatinib to the mESCs culture at an appropriate dose and in a timely manner could decrease chromosome stability without affecting pluripotency. Keywords Mouse embryonic stem cells · Paclitaxel · Lapatinib · Bortezomib · Chromosomal instability
Introduction Embryonic stem cells (ESCs) are established using preimplantation embryos. Chromosomal instability is a common phenomenon in preimplantation stage [1]. ESCs are suitable Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05903-8) contains supplementary material, which is available to authorized users. * Masood Bazrgar [email protected] 1
Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, No. 2, Hafez St., Banihashem St., Resalat Highway, P.O.Box:16635‑148, Tehran, Iran
2
Department of Genetics, Faculty of Biological Science, Shahid Beheshti University, Tehran, Iran
3
Department of Stem Cell and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
models for fundamental biological research, and their distinctive features make them a decent candidate for regenerative medicine [2–4].
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