Reproductive Hormones and Their Receptors May Affect Lung Cancer

Background/Aims: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. Methods: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E-2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ER alpha (oestrogen receptor alpha) and ER beta (oestrogen receptor beta) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ER alpha and ER beta were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. Results: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83 +/- 0.40 and 3.13 +/- 0.43, P < 0.05). T serum levels decreased exponentially in the ovariectomized group, while the E-2/T ratio increased compared with the control group (E-2: 55.88 +/- 11.45 and 78.21 +/- 9.37; T: 0.82 +/- 0.14 and 1.46 +/- 0.16; ratio: 69.62 +/- 14.43 +/- 29.81 and 52.22 +/- 5.42; all P < 0.05). The Western blot and IHC results indicated that AR, ER alpha and ER beta protein expression levels were obviously higher in transplanted tumour and lung tissues from the ovariectomized group, with particular increases in ER beta in transplanted tumour tissue and in ER alpha in lung tissue. The PCR results also showed markedly higher mRNA expression levels of AR, ER alpha and ER beta in the ovariectomized group, and in particular, ER beta in transplanted tumour tissue and ER alpha in lung tissue were significantly increased in the ovariectomized group. Conclusion: Ovariectomy decreased E-2 and T serum levels and increased the E-2/T ratio in mice, and this imbalance in the internal environment promoted the growth of transplanted tumours. Sex hormone disorder not only promoted transplanted tumour growth but also significantly reduced the protein and mRNA expression levels of sex hormone receptors. The metabolism of E-2 and T may affect the growth, proliferation and metabolism of lung cancer cells, and the mechanism by which sex hormones and their receptors influence lung cancer is worthy of further research. (C) 2017 The Author(s) Published by S. Karger AG, Basel