Combined Treatment with 2-Deoxy-D-Glucose and Doxorubicin Enhances the in Vitro Efficiency of Breast Cancer Radiotherapy.

Jalil Pirayesh Islamian,Alireza Farajollahi,Behzad Baradaran,Fahimeh Aghaee,Mona Fazel

doi:10.7314/apjcp.2015.16.18.8431

Jalil Pirayesh Islamian, Alireza Farajollahi + Show 3 more

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https://doi.org/10.7314/apjcp.2015.16.18.8431

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Abstract

Doxorubicin (DOX) was introduced as an effective chemotherapeutic for a wide range of cancers but with some severe side effects especially on myocardia. 2-Deoxy-D-glucose (2DG) enhances the damage caused by chemotherapeutics and ionizing radiation (IR) selectively in cancer cells. We have studied the effects of 1μM DOX and 500 μM 2DG on radiation induced cell death, apoptosis and also on the expression levels of p53 and PTEN genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays. DOX and 2DG treatments resulted in altered radiation-induced expression levels of p53 and PTEN genes in T47D as well as SKBR3 cells. In addition, the combination along with IR decreased the viability of both cell lines. The radiobiological parameter (D0) of T47D cells treated with 2DG/DOX and IR was 140 cGy compared to 160 cGy obtained with IR alone. The same parameters for SKBR3 cell lines were calculated as 120 and 140 cGy, respectively. The sensitivity enhancement ratios (SERs) for the combined chemo-radiotherapy on T47D and SKBR3 cell lines were 1.14 and 1.16, respectively. According to the obtained results, the combination treatment may use as an effective targeted treatment of breast cancer either by reducing the single modality treatment side effects.

Highlights

There are undeniable evidences on diversity of expression levels of oncogenes and suppressor genes in a cancer
We have studied the effects of 1μM DOX and 500 μM 2DG on radiation induced cell death, apoptosis and on the expression levels of p53 and phosphatase and tensin homologue (PTEN) genes in T47D and SKBR3 breast cancer cells irradiated with 100, 150 and 200 cGy x-rays
The results on the treatment induced apoptosis and Cytotoxic effects of combined doxorubicin and 2DG treatments followed by irradiation on breast cancer cell lines

Summary

Introduction

There are undeniable evidences on diversity of expression levels of oncogenes and suppressor genes in a cancer. The first pattern involved frequent mutations among the cell lines in genes from the same tumor suppressor pathway. These were included the p53 pathway in 90% of the cell lines (p53), the RB pathway in 64% (p16) and the PI3K pathway in 56% phosphatase and tensin homologue (PTEN) (Hollestelle et al, 2007). Gene protein expression level studies have demonstrated that, in breast cancer, there is an overexpression of PTEN in SKBR3 breast cancer cells, as with the estrogen receptor negative cancer cells, containing the wild-type PTEN and normal expression of p53. There is an overexpression of p53 in T47D breast cancer cells, as estrogen receptor positive cancer cells, containing wildtype p53 and normal expression of PTEN. In addition to inducing genes that drive apoptosis, p53 can activate the expression of genes that inhibits survival signaling (such as PTEN) or delay inhibitors of apoptosis (such as BIRC5) (Meek, 2004; Nakamura, 2004; Lu et al, 2005)

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