Several new chemotherapy agents are being tested in combination with radiation, but the best chemotherapy remains to be determined. The fate of irradiated cells is believed to be controlled by the network of signaling elements that lead to different modes of cell death or survival. Many stress-responsive genes are inducible by IR [18, 19]. These radiation-inducible genes are believed to have effects on the chemosensitivity RXDX-101 manufacturer of tumor cells [13, 20]. To determine the correlation between radio-RG7420 chemical structure resistance and sensitivity to chemotherapeutic drugs in esophageal cancer cells, we then analyzed the chemosensitivity of

EC109 and EC109/R cells with chemotherapeutic drugs cisplatin, 5-fluorouracil, doxorubicin, paclitaxel or etoposide. EC109/R, which survived 80 Gy irradiation, became more sensitive to different concentrations of 5-fluorouracil, doxorubicin, paclitaxel and etoposide, but maintained tolerance to cisplatin, as assessed by MTT assay (Figure 4). These findings suggest that cellular resistance to ionizing radiation have effects on the chemotherapeutic drug sensitivity in esophageal cancer cells. Several genes associated with cellular sensitivity to anticancer drugs have been selected for esophageal cancer. They were B4GALT5 (UDP-Gal: βGlcNAc β1,4-galactosyltransferase, polypeptide 5 gene), UGCG (UDP-glucose ceramide

glucosyltransferase gene), and XBP1 (X-box binding protein 1 gene) for 5-fluorouracil, A-1210477 NRCAM (neuronal cell adhesion molecule gene) for doxorubicin, ARFRP1 (ADP-ribosylation factor related protein 1 gene), IFITM1 (interferon induced transmembrane protein 1 gene), KIAA0685, and SIPA1L2 (signalinduced proliferation-associated 1 like 2 gene) for cisplatin [14]. Fractionated irradiation might induce cellular sensitivity related gene and protein expression in human tumor cell lines. The fact

that drug Florfenicol sensitivity is determined by multiple genes required a better understanding of the intricate network of the selected genes in the expression levels. Fractionated radiation treatment has also been reported to cause drug resistance in ovarian carcinoma cells [21] and ascites tumor cells [22]. It can induce functionally relevant multidrug resistance gene and protein expression in human tumor cell lines [13]. There are multiple factors that contribute to cisplatin resistance, but alterations of DNA repair processes have been known for some time to be important in mediating resistance [23, 24]. The most important DNA repair pathways involved in the cisplatin response are nucleotide excision repair (NER) and mismatch repair (MMR). MSI, which results from disorder of the MMR system and loss of MLH1 protein, is frequently induced during cisplatin-based chemotherapy [25]. Data have shown that suppression of ERCC1 expression enhances or restores cisplatin sensitivity, and combination of p53 inactivation and MMR deficiency results in cisplatin resistance [26].