This quasi-experimental study was conducted at Baqiyatallah university hospital between 2016 and 2017. The study protocol was registered at the ethics committee of Baqiyatallah University of Medical Sciences (Ref. No: IR.BMSU.REC.1395.17) and the Iranian Registry of Clinical Trials (IRCT20180 624040222N1). Three hundred and seventy men with prostate cancer were assessed for eligibility. Age between 50 and 75 years, not having any accompanying disease, the ability for quotidian activities and physical activity were considered as inclusion criteria. Patients with a history of smoking, hormone replacement therapy, physical activity, and training in the past six months were excluded from the study. These factors were assessed by the Physical Activity Readiness Questionnaire and medical history checklist.
After being informed of the study process and possible benefits and dangers of participation, patients signed an informed consent form. Patients were randomly allocated to two groups using a random number table: the first group underwent combined training and second group, as the control group didn’t. Patients were instructed on physical activities program in one session. BMI, maximal oxygen uptake, hip and waist circumference, waist to hip ratio (WHR) and fat percentage of participants were measured 48 hours before and after the intervention. All anthropometric and blood tests were performed, forty-eight hours prior to the start of the first training session and 48 hours after the last training session. All the measurements were taken by a single person. Jackson and Pollock's formula was used for calculating body fat density (17). Using the modified Bruce test and the non-direct measurement method, the maximum oxygen consumption was calculated (18).
At first, individuals ran for 10 minutes on the treadmill. After conducting stretch movements, individuals started resistance training with 40% of estimated maximum strength. Movements were ordered as leg extension, leg curls, lat pull-down and chest press with a 90-second rest and gradual increase in resistance. The maximum tolerated resistance was considered as the repeated resistance for the person. Individuals were encouraged verbally for being motivated. The study individuals had a 5 ml of their blood sampled in Baqiyatallah Hospital laboratory for measuring IGF-1 and IGFBP-3 level (ng/ml) using ZellBio GmbH kit (catalog No: ZB-10103S-H9648, Germany) by ELISA method.
Individuals of case group started training in Ghadir sports complex, Tehran, Iran. From the day after sampling, case individuals trained three sessions per week for eight weeks based on instructions of American College of Sports Medicine (ACSM) and by researcher-designed aerobic/resistance training (19). Each session lasted between 60-80 minutes including warming up and cooling down exercises. Thirty-seconds of dynamic stretch movements, at least 10 minutes, 3 to 4 times, were performed as cooling down movements. The resistance training program included four exercises for upper and lower limbs muscles with 60 to 70% of one repetition maximum (1RM) for three times with ten repetitions and 2 to 3-minutes rest between sets. Aerobic training was started with a 15-minute activity with a severity of 60% of VO_2max for three sessions in a week (Tables 1 and 2). Control group were asked not to have any sports activities during the study period. No changes were made in diet or medications of study individuals. Exit criteria were set as: three or more session absences, participation in other sports exercises, injuries, use of supplements or medications without the permission of the physician. Two days after the last session of training, laboratory and anthropometric factors were measured again and compared to pre-intervention measures.
 

Table 1. The performed aerobic training program in the present study on men with Prostate Cancer


Table 2. The performed resistance training program in the present study on men with Prostate Cancer

Data were analyzed using SPSS software version 21 (SPSS Inc., Chicago, IL). Normal distributed variables (approved by 1-sample Kolmogorov-Smirnov test) were compared using One Way ANCOVA test between the groups. The paired sample T-test was used to examine the significant difference between the beginning and the end of the period in each group. Mean, and standard deviation (SD) were used for describing categorical variables. A p value of less than 0.05 was considered statistically significant.

 

Mean level of IGF-1 was 6±1.04 ng/ml in control and 16.54±1.93 ng/ml in the training group before intervention. After the intervention, the control group had a mean IGF-1 level of 14.72±2.14 ng/ml while it was 12.15±1.94 in training group. Analysis showed a significant decrease in IGF-1 level in the training group (p=0.001, Figure 1) and a significant increase in IGF-1 level in the control group after intervention (p=0.001, Figure 1). There was a significant difference between training and control group for IGF-1 level after intervention (p=0.001, Figure 1 and Table 3).
 

Table 3. Results obtained from ANCOVA test for the between group comparisons for



Figure 1. Serum level variation of IGF-1. The letter A Indicates a significant difference between the pre-test and post-test in the training group. The letter B indicates a significant difference between the pre-test and post-test in the control group. * Simply illustrates a meaningful difference between training and control groups at the end of the trial.
 

Mean level of IGFBP-3 was 2.79±0.74 ng/ml in control and 1.69±0.12 ng/ml in the training group before intervention. After the intervention, the control group had a mean IGFBP-3 level of 2.16±0.26 ng/ml while it was 5.34±1.38 in training group. Analysis showed a significant increase in IGFBP-3 level in the training group (p=0.001, Figure 2). There was a significant difference between training and control group for IGFBP-3 level after intervention (p=0.036, Figure 2).
 

Figure 2. Serum level variation of IGFBP-3. The letter A Indicates a significant difference between the pre-test and post-test in the training group. The letter * Indicates a significant difference between the training group and the control group at the end of the trial.

Discussion

The results of this study indicate that an eight-week period of combined training (aerobic-resistance)  are likely to affect some of the factors associated with prostate cancer which in turn may be able to contribute to the improvement of patients with prostate cancer (along with the main treatment protocol). We found that an eight-week period of combined training (aerobic-resistance) can significantly decrease the IGF-1 level in the training group. On the other hand, Tofighi et al. (2012) found that an eight-week period of resistance training can decrease IGF-1 level more than resistance and combined training (20).
Seo et al. (2010) showed that combined and aerobic training might increase anabolic hormones like growth hormone and IGF-1 in senior women. They also argued that combined trainings was more effective on the secretion of anabolic hormones than aerobic trainings, which contradicts the results of this study (21). The variances may be attributable to differences in gender, training protocol or accuracy of measurement tools. Rosendal (2002) found that IGF-1 decreases in non-trained control individuals after 11 weeks of physical activity (22). Primary preparedness of individuals, training protocol, the severity of training and duration of rest may be reasons for the difference. It has been reported that physical activity, especially resistance training, may have effects on IGF axis proteins (23). Resistance training can increase IGF-1 level through increasing IGF-1 gene transcription; however, a direct relationship has been approved between BMI and IGF-1 (23). Another possible mechanism is PI3K cascade which accelerates cell proliferation and mitosis and inhibits apoptosis. Cascade activity is dependent on insulin level, and physical activity decreased insulin level in case group; so, this decrease has resulted in inhibition or decrease in PI3K flow (24). IGF-1 stimulates phosphorylation of PI3K which itself activates phospholipid phosphatase. This enzyme inhibits apoptosis and results in cell proliferation (11).
Experimental studies have shown that high levels of IGF-1 are related to prostate cancer (5). Also, high levels of IGF-1 have been related to the risk of prostate cancer in three prospective studies (25). Regular physical activity may potentially postpone metastasis by changing IGF axis factors. Specialists believe that severe physical activity slows prostate cancer developments and decreases mortality (26). Tang et al. showed a significant decrease in the growth of LNCaP cells cultured in the serum of men under diet and physical activity interventions (27). They also reported that LNCaP cells growth decreased following the increase of IGFBP-1 and decrease of IGF-1 after training (27). Singh et al. (1999) showed that weight training in older adults increases muscle power and IGF-1 level (28). In Tung et al. (2002) study, an 11-day period of aerobic trainings decreased IGF-1 level as 60 ng and 170 ng in a group which performed aerobic trainings for 14 years (27).
Biochemical studies have shown that IGFBP-3 is a long-lived half-life protein which is dependent on variations in metabolic pathways (29). Hence, it seems that only by applying some interfering factors (i.e. resistance activity) over a long period will cause tangible changes in the protein. Nindl, et al. (2001)  Showed that applying a resistance activity for a long time by making changes in the pathways of metabolism would increase the production and release of IGFBP-3 immediately and in the recovery period after the resistance activity (30). It seems that the duration of the current research was suitable for resistance training, which has led to changes in the serum level of IGFBP-3 in the experimental group.
Louigi et al. (2002) reported that IGFBP-3 was significantly increased after an increase in growth hormone following exercise (31). Recent studies have emphasized the role of IGFBP-3 in the prevention of IGF-1 breakdown and lowering of free IGF-1 level (31). Researchers have shown that individuals with congenital growth hormone deficiency and low levels of IGF-1 have lower risks of breast, prostate, colon, gastric, liver, pancreas, ovary, thyroid, brain and uterus cancers (32). Previous studies found that higher levels of IGF-1and low levels of IGFBP-3 increase risk of prostate cancer development (33). Khosravi et al  reported that the highest level of IGFBP-3 was found in healthy people followed by people with prostate cancer limited to prostate tissue; while the lowest IGFBP-3 level was in patients with prostate cancer bone metastasis (34).

 

Conclusion

The Findings of the present study showed that eight weeks of the combined training program in men with prostate cancer, significantly decreased their IGF-1 level. Also, IGFBP-3 level was significantly increased in the experimental group. It seems that using these training programs in a precise period maybe beneficial in prevention of prostate cancer development beside special treatment protocols. Several factors seem to be effective in research outcomes. Factors such as age, sex, race, overweight, stage of disease, type of exercises, training records and initial level of preparation, severity, and duration of exercises, and even psychological issues can affect the results. It is therefore recommended that these factors be considered in order to interpret and generalize the results. What is noteworthy is that most studies have stated the positive effects of exercise on related factors affecting diseases such as cancer. What is more important is to find out which exercises, along with the main treatment protocol, are appropriate and can improve the likelihood of recovery and ultimately improve the patient’s quality of life. Answer to these questions will require further research in this regard.

 

Acknowledgements

We would like to thank the clinical research development unit of Baqiyatallah hospital for helping us with this research.

 

Conflicts of Interest

This The authors declared no conflicts of interest.

Funding

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