In recent years, A few research have reported that indomethacin has a sensitization and drug-resistant role [2
]. At the same time, indomethacin may affect the tumor cell growth cycle, preventing increasement and inducing apoptosis. It could update immune status and stimulate the body to produce tumor necrosis factor (TNF), interleukin (IL)-2, and interferon(INF) factors. Thus, it could have both a direct anti-tumor effect and assist in anti-tumor functions of other agents [6
With the development of nuclear imaging technology, ARG has played an important role in the understanding of the effects of radioactive drugs at the cellular and sub-cellular levels. It played an important role in researching the metabolism and toxicology evaluations. It could also assist in designing a clinical treatment plan. In addition to its role for radioactive isotopes [9
], ARG also has biological characteristics, which can be used to observe the quantitative distribution and exact positioning of the cell, according to its biological metabolism. LiKun Zhou [10
] et al applied tritium-labeled indomethacin and found indomethacin could focus on the cell membrane, cytoblastema, and nucleus. Our study used 131
I-His-IN in mice, with the ARG slices, finding the drug targeted at the cell membrane, cell cytoplasm, and the nucleus. The drug mainly distributed in the cytoplasm and nucleus. This result was similar to an earlier report [10
]. Research by ChunMei Chen [11
] showed that indomethacin can penetrate the bi-layer of the cell membrane structure into tumor cells in the cytoplasm and even the nucleus. Based on this finding, indomethacin may also have an anti-tumor role in the membrane, cytoplasm, and the nucleus. In the cytoplasm, indomethacin may target the mitochondria directly, affecting its energy metabolism or through oxidative phosphorylation to affect the mitochondrial indirectly.
Other research [12
] has shown that indomethacin may work on drug resistance by inducing apoptosis, influencing the energy metabolism of the mitochondria, especially oxidative phosphorylation. This latter effect may increase the activity of oxygen by blocking the oxidative phosphorylation, since the activity of oxygen was an important factor in suppressing tumor growth. Jiu bo Cai [13
] reported indomethacin could reverse lung cancer cell drug resistance by improving 99
intake A549 /DDP and inhibit MDRL and Pg-P expression.
The data of our research indicated that 131
I-His-IN was mostly distributed in the blood, liver, kidney, and tumor tissue. At 8 hours, the distribution of radioactivity in tumor tissue reached its peak (52%). The distribution of radioactivity were differently among organs. At 72 hours, the radioactive count was reduced significantly, and this may be related to the short physical and biological half-life of 131
iodine. Kanfeng Liu [14
] also reported that 131
I-His-IN was absorbed in the stomach and then absorbed and stored in tumor tissues and excreted via the kidney.
In our study, in PET-CT groups, the SUVmax was greater than 2.5 (at 4.3 ±1.3) for the tumor tissue location before treatment. After 7 days of treatment, 2 days later the mice underwent 18 F-FDG PET-CT scanning again, 18F-FDG uptake of the ROI in the tumor site decreased greatly. The SUVmax of the treated groups (3.73 + 0.58) were lower than the control group (5. 3 + 0.43).
Our data suggested the SUVmax among the treatment groups reduced differently, with 131
I-His-IN decreasing significantly (F = 6.54, P < 0.05). This showed that 131
I-His-IN inhibited tumor cells may through both chemotherapy and radiation. The possible mechanisms may include: indomethacin can gather specific nuclide into tumor cells or on its surface as the carrier. At the same time 131
I emits nuclear rays (β
particles) aimed at tumor tissue, killing the cancer cells; Indomethacin may inhibit tumor chemical toxicity and enhance the nuclide ionizing radiation effect. In the future, further study may fucus on radiation-chemical-biological therapy complexes, which would provide triple therapy to the tumor locally. In addition, 131
I could release γ rays, which comprise single-photon emission computed tomography (SPECT) imaging for tumor tissue [14
The half-life of 131I is 8.06 days, which is helpful for transportation and clinical application. In the procession of decay, β、γ rays may be released, whose mainly energy at 610 keV and 364 keV spectively. Indomethacin could carry 131I and aim it in the tumor site for a long time, which preventing the damage to normal tissue or other organs greatly, If 131 I-Hi-IN could be made into anti-tumor targeting probe, which will become a hot point for radiation therapy research.
Serum VEGF could be used in diagnosis, evaluation before surgery, and monitoring of effective treatment and prognosis for lung cancer. Angiogenesis is the growth and metastasis of cells and the anatomical and physiological basis for lung cancer. To inhibit angiogenesis is key in controlling invasion and metastasis of cancer cells and this inhibition could improve the prognosis and survival rates for patients. Studies [15
] have confirmed that VEGF has a high expression in non-small cell and small cell lung cancers. TianGang Xie et al [17
] confirmed a high level of expression of VEGF in peripheral blood for lung cancer patients using ELISA methods. The preoperative level was statistically different compared with a normal control group. Yang Dong Xia et al [18
] research showed that VEGF mainly expressed in the cytoplasm of lung cancer cells, it showed a clear heterogeneity. It had a close relationship with tumor angiogenesis. In our research, in 131
I-His-IN group, VEGF contents decreased gradually over time. Statistical significance was seen among the different timepoints (F = 5.48, P < 0.05), especially at 0.5 and 48 hours (P < 0.05). VEGF levels were reduced in the treatment groups compared with the control group (F = 7.74, P < 0.05), with 131
I-His-IN and His-IN groups decreased greatly. These findings indicated that 131
I-His-IN may have an antitumor role by reducing VEGF level.