Efficacy of Different Sequences of Radio‐ and Chemotherapy in Experimental Models of Human Melanoma

Abstract

Although combination chemotherapy and radiotherapy have become the standard of care in numerous tumors, the mechanisms of interaction are often still unclear. The purpose of this study was to analyze the efficacy of radiation treatment and cisplatin sequences and to investigate their mechanisms of interaction. Three melanoma cell lines were used to evaluate in vitro radiation-induced cytotoxicity before and after cisplatin treatment. Expression levels of a panel of genes were determined by real-time RT-PCR. Cytotoxic effect was evaluated by flow cytometry analysis and Comet assay. We also used normal human dermal fibroblasts (HUDE) to evaluate the cytotoxicity of the two treatments by clonogenic assay. Radiation and cisplatin used singly were not particularly effective in reducing proliferation in melanoma cells. Conversely, radiation treatment followed by cisplatin showed a strong synergistic interaction in all cell lines, with a ratio index ranging from 16 to >100. The synergistic effect was accompanied by apoptosis induction (up to 40%) and an increase in the percentage of comet-shaped nucleoids from 85% to 99%. In parallel, our results also showed that radiation treatment of HUDE fibroblasts followed by cisplatin only induced weak cytotoxicity. Our findings highlight the efficacy of the sequence radiation → cisplatin in reducing cell proliferation and in inducing apoptosis in melanoma cell lines. This sequence also modulated a network of proteins involved in DNA damage repair.

Assessment of Oxaliplatin-Loaded Iodine Nanoparticles for Chemoradiotherapy of Human Colorectal Cancer (HT-29) Cells

“…Cancer remains a significant global health burden, and innovative chemoradiotherapy techniques are still required [ 21 , 22 , 23 ]. Radiation therapy is utilized in around 50% of all cancer therapies [ 24 ]; therefore, enhancing it would assist a large number of people.…”

Thermosensitive Hydrogel Co-loaded with Gold Nanoparticles and Doxorubicin for Effective Chemoradiotherapy

“…Cancer remains a major health burden throughout the world, and novel strategies in chemoradiotherapy are still needed (29)(30)(31). F127-based Au-DOX-Gel formulated and demonstrated its superior properties for intratumoral delivery.…”

“…Notably, the sensitive effect was less evident in HepG2 cells under 4 or 6 Gy radiation. These could be explained by the different radiosensitivities of different cells and by the different cellular uptake rates of AuNPs on different cells (48.5% for B16, 28.9% for HepG2 at 24 h) (4,29,39). Previous studies on cell viability were mostly carried out with X-ray dose constant or changed without a gradation (38).…”

Novel Instruments for the Implementation of Electrochemotherapy Protocols: From Bench Side to Veterinary Clinic

“…These results were substantiated by several studies in laboratory animals carrying spontaneous tumors or xenografts, showing that ECT could amplify the effectiveness of anticancer molecules as proven in vitro (Tsoneva et al, ; Meschini et al, ; Vásquez et al, ). Finally, this strategy has been successfully used to increase, both in vitro and in vivo, the delivery of DNA and RNA molecules within target cells, consequently, enhancing the tumor response to chemotherapy agents (Spugnini et al, , ; Guo et al, ; Arienti et al, ; Marrero et al, ; Spugnini and Baldi, ; Takei, ; Cutrera et al, ).…”