Asian Pacifc Journal of Cancer Prevention, Vol 16, 2015 8431 DOI:http://dx.doi.org/10.7314/APJCP.2015.16.18.8431 Enhancing the Effciency of Radiotherapy by Combined 2DG/DOX Treatment Asian Pac J Cancer Prev, 16 (18), 8431-8438 Introduction There are undeniable evidences on diversity of expression levels of oncogenes and suppressor genes in a cancer. Therefore, there wasn’t seen a constant response in a cancer for a therapy modality. Compilation of the mutation data were revealed two prevalent gene mutation patterns among the breast cancer cell lines (SKBR3 and T47D). The frst 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. Whereas, there is an overexpression of p53 in T47D breast cancer cells, as estrogen receptor positive cancer cells, containing wild- type p53 and normal expression of PTEN. In addition to inducing genes that drive apoptosis, p53 can also 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). 1 Department of Medical Physics, 2 Immunology Research center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran *For correspondence: pirayeshj@gmail.com 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. Keywords: 2DG - breast cancer - cell line - combined modality therapy - Doxorubicin RESEARCH ARTICLE Combined Treatment with 2-Deoxy-D-Glucose and Doxorubicin Enhances the in Vitro Effciency of Breast Cancer Radiotherapy Jalil Pirayesh Islamian 1 *, Fahimeh Aghaee 1 , Alireza Farajollahi 1 , Behzad Baradaran 2 , Mona Fazel 1 Also, PTEN, a dual specifcity PIP3 phosphatase that antagonizes AKT signaling, is capable of blocking MDM2 nuclear translocations, thus preventing the negative effects of growth factors on p53 activity. PTEN may also be viewed as a tumor suppressor. In the other hand, the induction of PTEN is essential for p53-mediated apoptosis so underscoring the importance of the AKT survival, signaled in determining the fnal outcomes of the p53 response. Consequently, p53 increases PTEN and PTEN decreases AKT activity. Breast tumors with a high levels of p53 expression are more frequently ER-negative and also with a higher proliferation rate and a poorer prognosis. The ER- positives, due to lack of p53 function, often respond poorly to radiation and chemotherapy. On the other hand, one of the major challenging problems in oncology, including chemotherapy, is the correlation of experimental and clinical data. The chemo-radiotherapy can have two strategic potentials. One potential is to eradicate tumor cells outside of the irradiated feld. This is defned as adjuvant use of the chemotherapeutics. So far, it does not assume any biological interaction occurring between the chemotherapeutics and ionizing radiation (IR), regarding to tumor cell killing. The second potential is to enhance the local control of radiotherapy. The clinician calls