Comparison of human lung cancer cell radiosensitivity after irradiations with therapeutic protons and carbon ions

Abstract

The aim of this study was to investigate effects of irradiations with the therapeutic proton and carbon ion beams in two non-small cell lung cancers, CRL5876 adenocarcinoma and HTB177 large cell lung carcinoma. The DNA damage response dynamics, cell cycle regulation, and cell death pathway activation were followed. Viability of both cell lines was lower after carbon ions compared to the therapeutic proton irradiations. HTB177 cells showed higher recovery than CRL5876 cells seven days following the treatments, but the survival rates of both cell lines were lower after exposure to carbon ions with respect to therapeutic protons. When analyzing cell cycle distribution of both CRL5876 and HTB177 cells, it was noticed that therapeutic protons predominantly induced G1 arrest, while the cells after carbon ions were arrested in G2/M phase. The results illustrated that differences in the levels of phosphorylated H2AX, a double-strand break marker, exist after therapeutic proton and carbon ion irradiations. We also observed dose-and time-dependent increase in the p53 and p21 levels after applied irradiations. Carbon ions caused larger increase in the quantity of p53 and p21 compared to therapeutic protons. These results suggested that various repair mechanisms were induced in the treated cells. Considering the fact that we have not observed any distinct change in the Bax/Bcl-2 ratio following irradiations, it seemed that different types of cell death were involved in the response to the two types of irradiations that were applied.

Gene expression profiling of breast cancer cell lines treated with proton and electron radiations

“…On the other hand, low LET radiations mainly cause DNA single strand breaks and indirect damage to macromolecules, due to the generation of reactive oxygen species and reactive nitric oxide species, which can both oxidate macromolecules and activate several intracellular signaling pathways, leading to stress responses and inflammation. 12,18,19,41,42 Here, we analyzed and compared molecular responses induced by conventional and non-conventional radiation treatment modalities (using electron and proton beams respectively), delivering the same dose of IR (9 Gy), in tumorigenic and nontumorigenic breast cell lines. In particular, we considered to use a sublethal proton radiation dose (9 Gy), which is able to mediate tumor changes in combination with immunotherapy, as recently described by Gameiro et al 8 We compared PRT-induced molecular changes with those activated by conventional RT.…”

Inhibition of Wnt signalling pathway by XAV939 enhances radiosensitivity in human cervical cancer HeLa cells

“…Recently, 12 C 6þ radiotherapy, as a highly intensive local therapy, has become one of the most used therapeutic strategies for various malignancies. Compared to conventional photon and proton irradiation, 12 C 6þ radiotherapy induces a stronger lethal effect on cancer cells due to the unique physical and biological effects, including superior physical dose distribution (spread-out Bragg peak) [5], smaller volume of irradiated normal tissue [6], higher relative biological effectiveness, lower oxygen enhancement ratio, unrepaired DNA damage and nearly unchanged radio-sensitivity within the cell cycle [7][8][9]. This results in a cell-killing effect that is two to three times greater than that of X-rays [5,10].…”

“…This results in a cell-killing effect that is two to three times greater than that of X-rays [5,10]. Accumulating evidence suggests that 12 C 6þ irradiation has been widely used in the treatment of a variety of cancers, such as pancreatic cancer [11], non-small cell lung cancer [12], locally advanced cervical cancer, prostate carcinoma [13] and breast cancer [14]. What is more, in the stage IVA patients of cervical carcinoma, 12 C 6þ beam radiotherapy has respectively shown a 3-year local control and overall survival rate of 66% and 47%, indicating that it can be applied to locally advanced cervical cancer [15].…”

DNA damage assessment of human breast and lung carcinoma cells irradiated with protons and carbon ions

“…They are more radioresistant to both types of radiation than HTB 177 cells, with SF2 values of 0.34 and 0.10, respectively. Serum starved HTB177 cells reveal the same level of radiosensitivity to protons and carbon ions as when they were grown in standard culture medium (Keta et al, 2017). Calculated RBE D10 values indicate higher effectiveness of carbon ions in terms of cell killing for both tested cell lines when compared to proton irradiations (2.13 vs. 1.47 for MCF-7 cells and 2.75 vs. 1.57 for HTB177 cells, Tables 1 and 2).…”