Although considerable knowledge of cancer biology has been acquired over the last few decades, cancer remains one of the major causes of mortality worldwide. Surgical resection is the most effective treatment; however, in the majority of cases, the tumor cells have already advanced locally or metastasized to distant organs by the time of diagnosis. Chemotherapy, a commonly used treatment for cancers that may not be removed by surgery, often results in severe side-effects due to the delivery of drugs to normal cells (1). As a result of these side-effects, the high doses of chemotherapy required to completely eradicate cancer cells are not tolerated in humans. In addition, the majority of cancer cells eventually acquire drug resistance and result in mortality. Therefore, the development of additional drugs or novel methods for the treatment of cancer is urgently required.

Radiation therapy is a highly targeted and effective way to treat certain types of cancer with limited metastasis (2). This treatment uses high-energy radiation, such as X-rays, γ-rays and charged particles. High-energy radiation induces double strand breaks in DNA, which promotes apoptosis of cancer cells (3). However, the radiation also results in severe damage to normal cells. Therefore, irradiation must be limited to the cancerous area to minimize the side-effects of this treatment. In contrast to these high-energy radiations, less energetic forms of radiation have not yet been fully evaluated for their anti-cancer functions. Near-infrared radiation (NIR) is a shorter wavelength of radiation in the infrared region of the spectrum, ranging between 750 and 2,500 nm. It has previously been reported that irradiation in the near-infrared region has multiple effects on cells. NIR induces the proliferation of keratinocytes (4), promotes cell attachment (5), attenuates the infarct size following myocardial infarction in rats and dogs (6,7) and regenerates and induces the proliferation of skeletal muscle (8). In addition, NIR has been demonstrated to have an inhibitory effect on advanced neoplasia (9). Broad-spectrum irradiation ranging between 1,100 and 1,800 nm resulted in apoptosis in multiple cancer cell types in vitro, independent of thermal energy (10). These previous studies have indicated that NIR may be useful for cancer treatment; however, additional studies are required to further confirm the effects of NIR on cancer cells. In the present study, a 915-nm laser was used to investigate the effects of NIR on pancreatic cancer cells.

In the present study, an automatic machine was used to irradiate pancreatic cancer cells with a 915-nm laser, and the effects of irradiation on pancreatic cancer cells were examined. A significant induction of apoptosis was observed with increasing power and duration of the irradiation. The irradiation laser induced temperature increases in the media; however, it appears that apoptosis was induced by irradiation and not thermal energy. Suppression of tumor cell proliferation requires an exposure for ≥60 min to high temperatures of ~42°C (11). In the present study, the cells were incubated at 25°C prior to the irradiation. Therefore, a temperature increase of ~10°C induced by the irradiation would not be sufficient to induce apoptosis of the cells. In accordance with the results of the present study, previous studies have demonstrated that NIR resulted in reduced cell proliferation and apoptosis in multiple cell lines, independent of the thermal energy (10,12,13).

Low-energy non-ionizing radiation is known to affect numerous cellular activities by modulating electrochemical systems in cells, such as the modulation of mitochondrial signaling by NIR (14,15). Cytochrome c oxidase is an enzyme that mediates the transfer of electrons from cytochrome c to molecular oxygen (16). The oxidase is a receptor of NIR and activates mitochondrial signaling in mammalian cells (17,18). Differentiation of neural progenitor cells is also promoted by NIR. The radiation induces the production of ATP, which subsequently activates P2Y receptors for neurite outgrowth (19). Although the molecular mechanisms by which low-energy radiation affects various cellular activities are unclear, accumulating evidence indicates that NIR may be used in multiple clinical treatments (6–10). A number of previous studies have indicated the possible use of low-energy radiation for cancer treatment (9,10). NIR elicited selective cytotoxic effects on tumor tissues (20,21). Although the exact molecular mechanisms of how NIR exerts cytotoxic effects is not clear, a previous study indicated that double strand breaks in DNA are associated with apoptosis induction (22). NIR has been demonstrated to activate the DNA damage checkpoint pathway, resulting in cell cycle arrest in G2/M phase or the induction of apoptosis (23). These previous studies have indicated that NIR may be used for cancer treatment in combination with ionizing radiation or chemotherapeutic agents.

In the present study, pancreatic cancer cells were used to examine the effects of NIR. Pancreatic cancer is one of the most aggressive types of human cancer and is the leading cause of cancer-associated mortality (24,25). Gemcitabine is currently the standard treatment for advanced or resected pancreatic cancer (26). However, since a large number of patients are resistant to gemcitabine treatment, this drug provides only modest survival benefits. In the present study, the combination of NIR and gemcitabine was more effective than either single treatment alone. Although it is not technically easy to directly irradiate pancreatic cancer, the development of such devices may be useful for the treatment of pancreatic cancer. Additional investigation into the development of NIR therapy may contribute to an improved prognosis for patients with cancer.